![NcRNAs-central-dogma](https://upload.wikimedia.org/wikipedia/commons/e/e6/NcRNAs-central-dogma.svg)
A non-coding RNA (ncRNA) is a functional
RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
molecule that is not
translated
Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...
into a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
. The
DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
. Abundant and functionally important
types of non-coding RNAs include
transfer RNA
Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino ac ...
s (tRNAs) and
ribosomal RNA
Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal ...
s (rRNAs), as well as small RNAs such as
microRNA
MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRN ...
s,
siRNA
Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA at first non-coding RNA molecules, typically 20-24 (normally 21) base pairs in length, similar to miRNA, and operating wi ...
s,
piRNA
Pirna (; hsb, Pěrno; ) is a town in Saxony, Germany and capital of the administrative district Sächsische Schweiz-Osterzgebirge. The town's population is over 37,000. Pirna is located near Dresden and is an important district town as well as ...
s,
snoRNA
In molecular biology, Small nucleolar RNAs (snoRNAs) are a class of small RNA molecules that primarily guide chemical modifications of other RNAs, mainly ribosomal RNAs, transfer RNAs and small nuclear RNAs. There are two main classes of snoRNA, ...
s,
snRNA
Small nuclear RNA (snRNA) is a class of small RNA molecules that are found within the splicing speckles and Cajal bodies of the cell nucleus in eukaryotic cells. The length of an average snRNA is approximately 150 nucleotides. They are transcri ...
s,
exRNAs,
scaRNAs
Small Cajal body-specific RNAs (scaRNAs) are a class of small nucleolar RNAs (snoRNAs) that specifically localise to the Cajal body, a nuclear organelle (cellular sub-organelle) involved in the biogenesis of small nuclear ribonucleoproteins (sn ...
and the
long ncRNAs such as
Xist and
HOTAIR
HOTAIR (for HOX transcript antisense RNA) is a human gene located between HOXC11 and HOXC12 on chromosome 12. It is the first example of an RNA expressed on one chromosome that has been found to influence transcription of HOXD cluster posterio ...
.
The number of non-coding RNAs within the human genome is unknown; however, recent
transcriptomic
Transcriptomics technologies are the techniques used to study an organism's transcriptome, the sum of all of its RNA transcripts. The information content of an organism is recorded in the DNA of its genome and expressed through transcription. He ...
and
bioinformatic
Bioinformatics () is an interdisciplinary field that develops methods and software tools for understanding biological data, in particular when the data sets are large and complex. As an interdisciplinary field of science, bioinformatics combine ...
studies suggest that there are thousands of non-coding transcripts.
Many of the newly identified ncRNAs have not been validated for their function.
There is no consensus in the literature on how much of non-coding transcription is functional. Some researchers have argued that many ncRNAs are non-functional (sometimes referred to as "junk RNA"), spurious transcriptions.
Others, however, disagree, arguing instead that many non-coding transcripts do have functions and that those functions are being and will continue to be discovered.
History and discovery
Nucleic acid
Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main cl ...
s were first discovered in 1868 by
Friedrich Miescher
Johannes Friedrich Miescher (13 August 1844 – 26 August 1895) was a Swiss physician and biologist. He was the first scientist to isolate nucleic acid in 1869. He also identified protamine and made a number of other discoveries.
Miescher had is ...
, and by 1939, RNA had been implicated in
protein synthesis
Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...
. Two decades later,
Francis Crick
Francis Harry Compton Crick (8 June 1916 – 28 July 2004) was an English molecular biologist, biophysicist, and neuroscientist. He, James Watson, Rosalind Franklin, and Maurice Wilkins played crucial roles in deciphering the helical struc ...
predicted a functional RNA component which mediated
translation
Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...
; he reasoned that RNA is better suited to base-pair with an mRNA transcript than a pure
polypeptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A p ...
.
The first non-coding RNA to be characterised was an
alanine
Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side c ...
tRNA found in
baker's yeast
Baker's yeast is the common name for the strains of yeast commonly used in baking bread and other bakery products, serving as a leavening agent which causes the bread to rise (expand and become lighter and softer) by converting the fermentable ...
, its structure was published in 1965.
To produce a purified alanine tRNA sample,
Robert W. Holley
Robert William Holley (January 28, 1922 – February 11, 1993) was an American biochemist. He shared the Nobel Prize in Physiology or Medicine in 1968 (with Har Gobind Khorana and Marshall Warren Nirenberg) for describing the structure of alani ...
''et al.'' used 140
kg of commercial baker's yeast to give just 1
g of purified tRNA
Ala for analysis.
The 80
nucleotide
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...
tRNA was sequenced by first being digested with
Pancreatic ribonuclease
Pancreatic ribonuclease family (, ''RNase'', ''RNase I'', ''RNase A'', ''pancreatic RNase'', ''ribonuclease I'', ''endoribonuclease I'', ''ribonucleic phosphatase'', ''alkaline ribonuclease'', ''ribonuclease'', ''gene S glycoproteins'', ''Ceratit ...
(producing fragments ending in
Cytosine
Cytosine () ( symbol C or Cyt) is one of the four nucleobases found in DNA and RNA, along with adenine, guanine, and thymine (uracil in RNA). It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached (an am ...
or
Uridine
Uridine (symbol U or Urd) is a glycosylated pyrimidine analog containing uracil attached to a ribose ring (or more specifically, a ribofuranose) via a β-N1-glycosidic bond. The analog is one of the five standard nucleosides which make up nuclei ...
) and then with takadiastase ribonuclease Tl (producing fragments which finished with
Guanosine
Guanosine (symbol G or Guo) is a purine nucleoside comprising guanine attached to a ribose (ribofuranose) ring via a β-N9-glycosidic bond. Guanosine can be phosphorylated to become guanosine monophosphate (GMP), cyclic guanosine monophosphate (c ...
).
Chromatography
In chemical analysis, chromatography is a laboratory technique for the separation of a mixture into its components. The mixture is dissolved in a fluid solvent (gas or liquid) called the ''mobile phase'', which carries it through a system (a ...
and identification of the 5' and 3' ends then helped arrange the fragments to establish the RNA sequence.
Of the three structures originally proposed for this tRNA,
the 'cloverleaf' structure was independently proposed in several following publications.
The cloverleaf
secondary structure
Protein secondary structure is the three dimensional conformational isomerism, form of ''local segments'' of proteins. The two most common Protein structure#Secondary structure, secondary structural elements are alpha helix, alpha helices and beta ...
was finalised following
X-ray crystallography
X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
analysis performed by two independent research groups in 1974.
Ribosomal RNA
Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal ...
was next to be discovered, followed by URNA in the early 1980s. Since then, the discovery of new non-coding RNAs has continued with
snoRNAs
In molecular biology, Small nucleolar RNAs (snoRNAs) are a class of small RNA molecules that primarily guide chemical modifications of other RNAs, mainly ribosomal RNAs, transfer RNAs and small nuclear RNAs. There are two main classes of snoRNA, ...
,
Xist,
CRISPR
CRISPR () (an acronym for clustered regularly interspaced short palindromic repeats) is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. These sequences are derived from DNA fragments of bacte ...
and many more.
Recent notable additions include
riboswitch
In molecular biology, a riboswitch is a regulatory segment of a messenger RNA molecule that binds a small molecule, resulting in a change in production of the proteins encoded by the mRNA. Thus, an mRNA that contains a riboswitch is directly invo ...
es and
miRNA
MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRN ...
; the discovery of the RNAi
mechanism
Mechanism may refer to:
* Mechanism (engineering), rigid bodies connected by joints in order to accomplish a desired force and/or motion transmission
*Mechanism (biology), explaining how a feature is created
*Mechanism (philosophy), a theory that ...
associated with the latter earned
Craig C. Mello and
Andrew Fire
Andrew Zachary Fire (born April 27, 1959) is an American biologist and professor of pathology and of genetics at the Stanford University School of Medicine. He was awarded the 2006 Nobel Prize in Physiology or Medicine, along with Craig C. Mello ...
the 2006
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
.
Recent discoveries of ncRNAs have been achieved through both experimental and
bioinformatic methods.
Biological roles
Noncoding RNAs belong to several groups and are involved in many cellular processes.
These range from ncRNAs of central importance that are conserved across all or most cellular life through to more transient ncRNAs specific to one or a few closely related species. The more conserved ncRNAs are thought to be molecular fossils or relics from the
last universal common ancestor
The last universal common ancestor (LUCA) is the most recent population from which all organisms now living on Earth share common descent—the most recent common ancestor of all current life on Earth. This includes all cellular organisms; t ...
and the
RNA world
The RNA world is a hypothetical stage in the evolutionary history of life on Earth, in which self-replicating RNA molecules proliferated before the evolution of DNA and proteins. The term also refers to the hypothesis that posits the existence ...
, and their current roles remain mostly in regulation of information flow from DNA to protein.
In translation
Many of the conserved, essential and abundant ncRNAs are involved in
translation
Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...
.
Ribonucleoprotein
Nucleoproteins are proteins conjugated with nucleic acids (either DNA or RNA). Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins.
Structures
Nucleoproteins tend to be positively charged, facilitating in ...
(RNP) particles called
ribosome
Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ...
s are the 'factories' where translation takes place in the cell. The ribosome consists of more than 60%
ribosomal RNA
Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal ...
; these are made up of 3 ncRNAs in
prokaryotes
A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...
and 4 ncRNAs in
eukaryotes
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
. Ribosomal RNAs catalyse the translation of nucleotide sequences to protein. Another set of ncRNAs,
Transfer RNA
Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino ac ...
s, form an 'adaptor molecule' between
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
and protein. The
H/ACA box and C/D box snoRNAs are ncRNAs found in archaea and eukaryotes.
RNase MRP
RNase MRP (also called RMRP) is an enzymatically active ribonucleoprotein with two distinct roles in eukaryotes. RNAse MRP stands for RNAse for mitochondrial RNA processing. In mitochondria it plays a direct role in the initiation of mitochondri ...
is restricted to eukaryotes. Both groups of ncRNA are involved in the maturation of rRNA. The snoRNAs guide covalent modifications of rRNA, tRNA and
snRNA
Small nuclear RNA (snRNA) is a class of small RNA molecules that are found within the splicing speckles and Cajal bodies of the cell nucleus in eukaryotic cells. The length of an average snRNA is approximately 150 nucleotides. They are transcri ...
s; RNase MRP cleaves the
internal transcribed spacer 1
Internal transcribed spacer (ITS) is the spacer DNA situated between the small-subunit ribosomal RNA (rRNA) and large-subunit rRNA genes in the chromosome or the corresponding transcribed region in the polycistronic rRNA precursor transcript.
I ...
between 18S and 5.8S rRNAs. The ubiquitous ncRNA,
RNase P
Ribonuclease P (, ''RNase P'') is a type of ribonuclease which cleaves RNA. RNase P is unique from other RNases in that it is a ribozyme – a ribonucleic acid that acts as a catalyst in the same way that a protein-based enzyme would. Its f ...
, is an evolutionary relative of RNase MRP.
RNase P matures tRNA sequences by generating mature 5'-ends of tRNAs through cleaving the 5'-leader elements of precursor-tRNAs. Another ubiquitous RNP called
SRP recognizes and transports specific nascent proteins to the
endoplasmic reticulum
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
in
eukaryote
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
s and the
plasma membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
in
prokaryote
A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...
s. In bacteria,
Transfer-messenger RNA (tmRNA) is an RNP involved in rescuing stalled ribosomes, tagging incomplete
polypeptides
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A p ...
and promoting the degradation of aberrant mRNA.
In RNA splicing
![Yeast tri-snRNP](https://upload.wikimedia.org/wikipedia/commons/1/18/Yeast_tri-snRNP.jpg)
In eukaryotes, the
spliceosome
A spliceosome is a large ribonucleoprotein (RNP) complex found primarily within the nucleus of eukaryotic cells. The spliceosome is assembled from small nuclear RNAs (snRNA) and numerous proteins. Small nuclear RNA (snRNA) molecules bind to specifi ...
performs the
splicing reactions essential for removing
intron
An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene. ...
sequences, this process is required for the formation of mature
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
. The
spliceosome
A spliceosome is a large ribonucleoprotein (RNP) complex found primarily within the nucleus of eukaryotic cells. The spliceosome is assembled from small nuclear RNAs (snRNA) and numerous proteins. Small nuclear RNA (snRNA) molecules bind to specifi ...
is another RNP often known as the
snRNP
snRNPs (pronounced "snurps"), or small nuclear ribonucleoproteins, are RNA-protein complexes that combine with unmodified pre-mRNA and various other proteins to form a spliceosome, a large RNA-protein molecular complex upon which splicing of pre- ...
or tri-snRNP. There are two different forms of the spliceosome, the major and minor forms. The ncRNA components of the major spliceosome are
U1,
U2,
U4,
U5, and
U6. The ncRNA components of the minor spliceosome are
U11,
U12,
U5,
U4atac and
U6atac.
Another group of introns can catalyse their own removal from host transcripts; these are called self-splicing RNAs. There are two main groups of self-splicing RNAs:
group I catalytic intron
Group I introns are large self-splicing ribozymes. They catalyze their own excision from mRNA, tRNA and rRNA precursors in a wide range of organisms. The core secondary structure consists of nine paired regions (P1-P9). These fold to essentially ...
and
group II catalytic intron. These ncRNAs catalyze their own excision from mRNA, tRNA and rRNA precursors in a wide range of organisms.
In mammals it has been found that snoRNAs can also regulate the
alternative splicing
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be ...
of mRNA, for example snoRNA
HBII-52 regulates the splicing of
serotonin receptor 2C.
In nematodes, the
SmY ncRNA appears to be involved in mRNA
trans-splicing
''Trans''-splicing is a special form of RNA processing where exons from two different primary RNA transcripts are joined end to end and ligated. It is usually found in eukaryotes and mediated by the spliceosome, although some bacteria and archaea ...
.
In DNA replication
Y RNA
Y RNAs are small non-coding RNAs. They are components of the Ro60 ribonucleoprotein particle which is a target of autoimmune antibodies in patients with systemic lupus erythematosus. They are also reported to be necessary for DNA replication thr ...
s are stem loops, necessary for
DNA replication
In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritanc ...
through interactions with
chromatin
Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...
and initiation proteins (including the
origin recognition complex
In molecular biology, origin recognition complex (ORC) is a multi-subunit DNA binding complex (6 subunits) that binds in all eukaryotes and archaea in an ATP-dependent manner to origins of replication. The subunits of this complex are encoded ...
).
They are also components of the
Ro60 ribonucleoprotein particle which is a target of autoimmune antibodies in patients with
systemic lupus erythematosus
Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...
.
In gene regulation
The
expression
Expression may refer to:
Linguistics
* Expression (linguistics), a word, phrase, or sentence
* Fixed expression, a form of words with a specific meaning
* Idiom, a type of fixed expression
* Metaphorical expression, a particular word, phrase, o ...
of many thousands of
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
s are regulated by ncRNAs. This regulation can occur in
trans
Trans- is a Latin prefix meaning "across", "beyond", or "on the other side of".
Used alone, trans may refer to:
Arts, entertainment, and media
* Trans (festival), a former festival in Belfast, Northern Ireland, United Kingdom
* ''Trans'' (film ...
or in
cis
Cis or cis- may refer to:
Places
* Cis, Trentino, in Italy
* In Poland:
** Cis, Świętokrzyskie Voivodeship, south-central
** Cis, Warmian-Masurian Voivodeship, north
Math, science and biology
* cis (mathematics) (cis(''θ'')), a trigonome ...
. There is increasing evidence that a special type of ncRNAs called
enhancer RNAs
Enhancer RNAs (eRNAs) represent a class of relatively long non-coding RNA molecules (50-2000 nucleotides) transcribed from the DNA sequence of enhancer regions. They were first detected in 2010 through the use of genome-wide techniques such as RN ...
, transcribed from the enhancer region of a gene, act to promote gene expression.
Trans-acting
In higher eukaryotes
microRNA
MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRN ...
s regulate gene expression. A single miRNA can reduce the expression levels of hundreds of genes. The mechanism by which mature miRNA molecules act is through partial complementary to one or more messenger RNA (mRNA) molecules, generally in
3' UTRs. The main function of miRNAs is to down-regulate gene expression.
The ncRNA
RNase P
Ribonuclease P (, ''RNase P'') is a type of ribonuclease which cleaves RNA. RNase P is unique from other RNases in that it is a ribozyme – a ribonucleic acid that acts as a catalyst in the same way that a protein-based enzyme would. Its f ...
has also been shown to influence gene expression. In the human nucleus,
RNase P
Ribonuclease P (, ''RNase P'') is a type of ribonuclease which cleaves RNA. RNase P is unique from other RNases in that it is a ribozyme – a ribonucleic acid that acts as a catalyst in the same way that a protein-based enzyme would. Its f ...
is required for the normal and efficient transcription of various ncRNAs transcribed by
RNA polymerase III
In eukaryote cells, RNA polymerase III (also called Pol III) is a protein that transcribes DNA to synthesize ribosomal 5S rRNA, tRNA and other small RNAs.
The genes transcribed by RNA Pol III fall in the category of "housekeeping" genes whose e ...
. These include tRNA,
5S rRNA,
SRP RNA, and
U6 snRNA
U6 snRNA is the non-coding small nuclear RNA (snRNA) component of U6 snRNP (''small nuclear ribonucleoprotein''), an RNA-protein complex that combines with other snRNPs, unmodified pre-mRNA, and various other proteins to assemble a spliceosome, ...
genes. RNase P exerts its role in transcription through association with Pol III and
chromatin
Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...
of active tRNA and 5S rRNA genes.
It has been shown that
7SK RNA
In molecular biology 7SK is an abundant small nuclear RNA found in metazoans. It plays a role in regulating transcription by controlling the positive transcription elongation factor P-TEFb. 7SK is found in a small nuclear ribonucleoprotein c ...
, a
metazoan
Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, are able to move, can reproduce sexually, and go through an ontogenetic stage in ...
ncRNA, acts as a negative regulator of the
RNA polymerase II
RNA polymerase II (RNAP II and Pol II) is a multiprotein complex that transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNAP enzymes found in the nucleus of eukaryoti ...
elongation factor P-TEFb, and that this activity is influenced by stress response pathways.
The bacterial ncRNA,
6S RNA
In the field of molecular biology the 6S RNA is a non-coding RNA that was one of the first to be identified and sequenced. What it does in the bacterial cell was unknown until recently. In the early 2000s scientists found out the function of 6S ...
, specifically associates with RNA polymerase holoenzyme containing the
sigma70 specificity factor. This interaction represses expression from a sigma70-dependent
promoter during
stationary phase.
Another bacterial ncRNA,
OxyS RNA
OxyS RNA is a small non-coding RNA which is induced in response to oxidative stress in ''Escherichia coli''. This RNA acts as a global regulator to activate or repress the expression of as many as 40 genes, by an antisense mechanism, including the ...
represses translation by binding to Shine-Dalgarno sequences thereby occluding ribosome binding. OxyS RNA is induced in response to oxidative stress in Escherichia coli.
The B2 RNA is a small noncoding RNA polymerase III transcript that represses mRNA transcription in response to heat shock in mouse
cells. B2 RNA inhibits transcription by binding to core Pol II. Through this interaction, B2 RNA assembles into preinitiation
complexes at the promoter and blocks RNA synthesis.
A recent study has shown that just the act of transcription of ncRNA sequence can have an influence on gene expression.
RNA polymerase II
RNA polymerase II (RNAP II and Pol II) is a multiprotein complex that transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNAP enzymes found in the nucleus of eukaryoti ...
transcription of ncRNAs is required for
chromatin
Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...
remodelling in the
Schizosaccharomyces pombe
''Schizosaccharomyces pombe'', also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically meas ...
. Chromatin is progressively converted to an open configuration, as several species of ncRNAs are transcribed.
Cis-acting
A number of ncRNAs are embedded in the 5'
UTRs (Untranslated Regions) of
protein coding genes and influence their expression in various ways. For example, a
riboswitch
In molecular biology, a riboswitch is a regulatory segment of a messenger RNA molecule that binds a small molecule, resulting in a change in production of the proteins encoded by the mRNA. Thus, an mRNA that contains a riboswitch is directly invo ...
can directly bind a
small target molecule; the binding of the target affects the gene's activity.
RNA leader sequences are found upstream of the first gene of amino acid biosynthetic operons. These
RNA elements form one of two possible structures in regions encoding very short peptide sequences that are rich in the end product amino acid of the operon. A terminator structure forms when there is an excess of the regulatory amino acid and ribosome movement over the leader transcript is not impeded. When there is a deficiency of the charged tRNA of the regulatory amino acid the ribosome translating the leader peptide stalls and the antiterminator structure forms. This allows RNA polymerase to transcribe the operon. Known RNA leaders are
Histidine operon leader
The Histidine operon leader is an RNA element found in the bacterial histidine operon. At least 6 amino acid operons are known to be regulated by attenuation
In physics, attenuation (in some contexts, extinction) is the gradual loss of flux ...
,
Leucine operon leader
The Leucine operon leader is an RNA element found upstream of the first gene in the Leucine biosynthetic operon. The leader sequence can assume two different secondary structures known as the terminator and the anti-terminator structure. The lea ...
,
Threonine operon leader
The threonine operon leader is an RNA element. Threonine is one of at least 6 amino acid operons are known to be regulated by attenuation. In each a leader sequence of 150–200 bp is found upstream of the first gene in the operon. This leader s ...
and the
Tryptophan operon leader.
Iron response element
In molecular biology, the iron response element or iron-responsive element (IRE) is a short conserved stem-loop which is bound by iron response proteins (IRPs, also named IRE-BP or IRBP). The IRE is found in UTRs (untranslated regions) of vari ...
s (IRE) are bound by
iron response proteins (IRP). The IRE is found in UTRs of various
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
s whose products are involved in
iron metabolism
Human iron metabolism is the set of chemical reactions that maintain human homeostasis of iron at the systemic and cellular level. Iron is both necessary to the body and potentially toxic. Controlling iron levels in the body is a critically impo ...
. When iron concentration is low, IRPs bind the ferritin mRNA IRE leading to translation repression.
Internal ribosome entry site An internal ribosome entry site, abbreviated IRES, is an RNA element that allows for translation initiation in a cap-independent manner, as part of the greater process of protein synthesis. In eukaryotic translation, initiation typically occurs at t ...
s (IRES) are
RNA structure
Nucleic acid structure refers to the structure of nucleic acids such as DNA and RNA. Chemically speaking, DNA and RNA are very similar. Nucleic acid structure is often divided into four different levels: primary, secondary, tertiary, and quatern ...
s that allow for
translation
Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...
initiation in the middle of a mRNA sequence as part of the process of
protein synthesis
Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...
.
In genome defense
Piwi-interacting RNA
Piwi-interacting RNA (piRNA) is the largest class of small non-coding RNA, non-coding RNA molecules expressed in animal cells. piRNAs form RNA-protein complexes through interactions with piwi-subfamily Argonaute proteins. These piRNA complexes are ...
s (piRNAs) expressed in
mammal
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
ian
testes
A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoster ...
and
somatic cell
A somatic cell (from Ancient Greek σῶμα ''sôma'', meaning "body"), or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Such cells compo ...
s form RNA-protein complexes with
Piwi
Piwi (or PIWI) genes were identified as regulatory proteins responsible for stem cell and germ cell differentiation. Piwi is an abbreviation of P-element Induced WImpy testis in ''Drosophila''. Piwi proteins are highly conserved RNA-bindi ...
proteins. These piRNA complexes (piRCs) have been linked to transcriptional gene silencing of
retrotransposon
Retrotransposons (also called Class I transposable elements or transposons via RNA intermediates) are a type of genetic component that copy and paste themselves into different genomic locations (transposon) by converting RNA back into DNA through ...
s and other genetic elements in
germ line
In biology and genetics, the germline is the population of a multicellular organism's cells that pass on their genetic material to the progeny (offspring). In other words, they are the cells that form the egg, sperm and the fertilised egg. They ...
cells, particularly those in
spermatogenesis
Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testis. This process starts with the mitotic division of the stem cells located close to the basement membrane of the tubule ...
.
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are repeats found in the
DNA of many
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
and
archaea
Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...
. The repeats are separated by spacers of similar length. It has been demonstrated that these spacers can be derived from phage and subsequently help protect the cell from infection.
Chromosome structure
Telomerase
Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres. A telomere is a region of repetitive sequences at each end of the chromosomes of most euka ...
is an RNP
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
that adds specific
DNA sequence repeats ("TTAGGG" in vertebrates) to
telomeric
A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature mos ...
regions, which are found at the ends of eukaryotic
chromosomes
A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
. The telomeres contain condensed DNA material, giving stability to the chromosomes. The enzyme is a
reverse transcriptase
A reverse transcriptase (RT) is an enzyme used to generate complementary DNA (cDNA) from an RNA template, a process termed reverse transcription. Reverse transcriptases are used by viruses such as HIV and hepatitis B to replicate their genomes, ...
that carries
Telomerase RNA, which is used as a template when it elongates telomeres, which are shortened after each
replication cycle.
Xist (X-inactive-specific transcript) is a long ncRNA gene on the
X chromosome
The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex-d ...
of the
placental mammals
Placental mammals (infraclass Placentalia ) are one of the three extant subdivisions of the class Mammalia, the other two being Monotremata and Marsupialia. Placentalia contains the vast majority of extant mammals, which are partly distinguishe ...
that acts as major effector of the
X chromosome inactivation
X-inactivation (also called Lyonization, after English geneticist Mary Lyon) is a process by which one of the copies of the X chromosome is inactivated in therian female mammals. The inactive X chromosome is silenced by being packaged into a ...
process forming
Barr bodies. An
antisense RNA
Antisense RNA (asRNA), also referred to as antisense transcript, natural antisense transcript (NAT) or antisense oligonucleotide, is a single stranded RNA that is complementary to a protein coding messenger RNA (mRNA) with which it hybridizes, and ...
,
Tsix
Tsix is a non-coding RNA gene that is antisense to the Xist RNA. Tsix binds Xist during X chromosome inactivation. The name Tsix comes from the reverse of Xist, which stands for X-inactive specific transcript.
Background
Female mammals have ...
, is a negative regulator of Xist. X chromosomes lacking Tsix expression (and thus having high levels of Xist transcription) are inactivated more frequently than normal chromosomes. In
drosophilids, which also use an
XY sex-determination system
The XY sex-determination system is a sex-determination system used to classify many mammals, including humans, some insects (''Drosophila''), some snakes, some fish (guppies), and some plants (''Ginkgo'' tree). In this system, the sex of an indi ...
, the
roX (RNA on the X) RNAs are involved in dosage compensation.
Both Xist and roX operate by
epigenetic
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
regulation of transcription through the recruitment of
histone-modifying enzymes
Histone-modifying enzymes are enzymes involved in the modification of histone substrates after protein translation and affect cellular processes including gene expression. To safely store the eukaryotic genome, DNA is wrapped around four core hi ...
.
Bifunctional RNA
''Bifunctional RNAs'', or ''dual-function RNAs'', are RNAs that have two distinct functions.
The majority of the known bifunctional RNAs are mRNAs that encode both a protein and ncRNAs. However, a growing number of ncRNAs fall into two different ncRNA categories; e.g.,
H/ACA box snoRNA and
miRNA
MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRN ...
.
Two well known examples of bifunctional RNAs are
SgrS RNA and
RNAIII
RNAIII is a stable 514 nt regulatory RNA transcribed by the P3 promoter of the '' Staphylococcus aureus'' quorum-sensing '' agr'' system ). It is the major effector of the ''agr'' regulon, which controls the expression of many '' S. aureus'' gene ...
. However, a handful of other bifunctional RNAs are known to exist (e.g., steroid receptor activator/SRA,
VegT RNA,
Oskar RNA,
ENOD40
''enod40'', also known as early nodulin 40, is a gene found in flowering plants. The gene has characteristics of both protein and Non-coding RNA genes. There is
some evidence that the non-coding characteristics of this gene are more widely conse ...
,
p53 RNA
and
SR1 RNA In molecular biology, the SR1 RNA is a Bacterial small RNA, small RNA (sRNA) produced by species of ''Bacillus'' and closely related bacteria. It is a dual-function RNA which acts both as a protein-coding RNA and as a regulatory sRNA.
SR1 RNA is i ...
. Bifunctional RNAs have recently been the subject of a special issue of
Biochimie.
As a hormone
There is an important link between certain non-coding RNAs and the control of hormone-regulated pathways. In ''
Drosophila
''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...
'', hormones such as
ecdysone
Ecdysone is a prohormone of the major insect molting hormone 20-hydroxyecdysone, which is secreted from the prothoracic glands. It is of steroidal structure. Insect molting hormones (ecdysone and its homologues) are generally called ecdysteroids. ...
and
juvenile hormone Juvenile hormones (JHs) are a group of acyclic sesquiterpenoids that regulate many aspects of insect physiology. The first discovery of a JH was by Vincent Wigglesworth. JHs regulate development, reproduction, diapause, and polyphenisms.The chem ...
can promote the expression of certain miRNAs. Furthermore, this regulation occurs at distinct temporal points within ''Caenorhabditis elegans'' development. In mammals,
miR-206
MiR-206 is a microRNA with a sequence conserved across most mammalian species, and in humans is a member of the myo-miR family of miRNAs, which includes miR-1, miR-133, and miR-208a/b. Mir-206 is well established for the regulation of cellular ...
is a crucial regulator of
estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
-receptor-alpha.
Non-coding RNAs are crucial in the development of several endocrine organs, as well as in endocrine diseases such as
diabetes mellitus
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
. Specifically in the MCF-7 cell line, addition of 17β-
estradiol
Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development of f ...
increased global transcription of the noncoding RNAs called lncRNAs near estrogen-activated coding genes.
In pathogenic avoidance
''
C. elegans
''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...
'' was shown to learn and inherit
pathogenic
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
avoidance after exposure to a single non-coding RNA of a
bacterial pathogen
Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and are often beneficial but others can cause infectious diseases. The number of ...
.
Roles in disease
As with
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s, mutations or imbalances in the ncRNA repertoire within the body can cause a variety of diseases.
Cancer
Many ncRNAs show abnormal expression patterns in
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
ous tissues.
These include
miRNAs
MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miR ...
,
long mRNA-like ncRNAs,
GAS5
Growth arrest-specific 5 is a non-protein coding RNA that in humans is encoded by the GAS5 gene.
GAS5 noncoding RNA, which accumulates in growth arrested cells, acts as a decoy hormone response element for the glucocorticoid receptor (GR) and he ...
,
SNORD50,
telomerase RNA and
Y RNA
Y RNAs are small non-coding RNAs. They are components of the Ro60 ribonucleoprotein particle which is a target of autoimmune antibodies in patients with systemic lupus erythematosus. They are also reported to be necessary for DNA replication thr ...
s.
The miRNAs are involved in the large scale regulation of many protein coding genes,
the Y RNAs are important for the initiation of DNA replication,
telomerase RNA that serves as a primer for telomerase, an RNP that extends
telomeric regions at chromosome ends (see
telomeres and disease for more information). The direct function of the long mRNA-like ncRNAs is less clear.
Germ-line
In biology and genetics, the germline is the population of a multicellular organism's cells that pass on their genetic material to the progeny (offspring). In other words, they are the cells that form the egg, sperm and the fertilised egg. Th ...
mutations in
miR-16-1 and
miR-15 primary precursors have been shown to be much more frequent in patients with
chronic lymphocytic leukemia
Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, nigh ...
compared to control populations.
It has been suggested that a rare
SNP (
rs11614913) that overlaps
hsa-mir-196a-2 has been found to be associated with
non-small cell lung carcinoma
Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to s ...
.
Likewise, a screen of 17 miRNAs that have been predicted to regulate a number of breast cancer associated genes found variations in the microRNAs
miR-17 and
miR-30c-1of patients; these patients were noncarriers of
BRCA1
Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a h ...
or
BRCA2
''BRCA2'' and BRCA2 () are a human gene and its protein product, respectively. The official symbol (BRCA2, italic for the gene, nonitalic for the protein) and the official name (originally breast cancer 2; currently BRCA2, DNA repair associated) ...
mutations, lending the possibility that familial breast cancer may be caused by variation in these miRNAs.
The
p53
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
tumor suppressor is arguably the most important agent in preventing tumor formation and progression. The p53 protein functions as a transcription factor with a crucial role in orchestrating the cellular stress response. In addition to its crucial role in cancer, p53 has been implicated in other diseases including diabetes, cell death after ischemia, and various neurodegenerative diseases such as Huntington, Parkinson, and Alzheimer. Studies have suggested that p53 expression is subject to regulation by non-coding RNA.
Another example of non-coding RNA dysregulated in cancer cells is the long non-coding RNA Linc00707. Linc00707 is upregulated and sponges miRNAs in human bone marrow-derived mesenchymal stem cells, in hepatocellular carcinoma, gastric cancer or breast cancer, and thus promotes osteogenesis, contributes to hepatocellular carcinoma progression, promotes proliferation and metastasis, or indirectly regulates expression of proteins involved in cancer aggressiveness, respectively.
Prader–Willi syndrome
The deletion of the 48 copies of the C/D box snoRNA
SNORD116 has been shown to be the primary cause of
Prader–Willi syndrome.
Prader–Willi is a developmental disorder associated with over-eating and learning difficulties. SNORD116 has potential target sites within a number of protein-coding genes, and could have a role in regulating alternative splicing.
Autism
The chromosomal locus containing the
small nucleolar RNA SNORD115 gene cluster has been duplicated in approximately 5% of individuals with
autistic traits.
A mouse model engineered to have a duplication of the SNORD115 cluster displays autistic-like behaviour.
A recent small study of post-mortem brain tissue demonstrated altered expression of long non-coding RNAs in the prefrontal cortex and cerebellum of autistic brains as compared to controls.
Cartilage–hair hypoplasia
Mutations within
RNase MRP
RNase MRP (also called RMRP) is an enzymatically active ribonucleoprotein with two distinct roles in eukaryotes. RNAse MRP stands for RNAse for mitochondrial RNA processing. In mitochondria it plays a direct role in the initiation of mitochondri ...
have been shown to cause
cartilage–hair hypoplasia
Cartilage–hair hypoplasia (CHH) is a rare genetic disorder. Symptoms may include short-limbed dwarfism due to skeletal dysplasia, variable level of immunodeficiency, and predisposition to cancer. It was first reported by Victor McKusick in 1965 ...
, a disease associated with an array of symptoms such as short stature, sparse hair, skeletal abnormalities and a suppressed immune system that is frequent among
Amish
The Amish (; pdc, Amisch; german: link=no, Amische), formally the Old Order Amish, are a group of traditionalist Anabaptist Christian church fellowships with Swiss German and Alsatian origins. They are closely related to Mennonite churches ...
and
Finnish
Finnish may refer to:
* Something or someone from, or related to Finland
* Culture of Finland
* Finnish people or Finns, the primary ethnic group in Finland
* Finnish language, the national language of the Finnish people
* Finnish cuisine
See also ...
.
The best characterised variant is an A-to-G
transition at nucleotide 70 that is in a loop region two bases 5' of a
conserved pseudoknot
__NOTOC__
A pseudoknot is a nucleic acid secondary structure containing at least two stem-loop structures in which half of one stem is intercalated between the two halves of another stem. The pseudoknot was first recognized in the turnip yellow ...
. However, many other mutations within RNase MRP also cause CHH.
Alzheimer's disease
The antisense RNA,
BACE1-AS is transcribed from the opposite strand to
BACE1
Beta-secretase 1, also known as beta-site amyloid precursor protein cleaving enzyme 1, beta-site APP cleaving enzyme 1 (BACE1), membrane-associated aspartic protease 2, memapsin-2, aspartyl protease 2, and ASP2, is an enzyme that in humans is enco ...
and is upregulated in patients with
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
.
BACE1-AS regulates the expression of BACE1 by increasing BACE1 mRNA stability and generating additional BACE1 through a post-transcriptional feed-forward mechanism. By the same mechanism it also raises concentrations of
beta amyloid
Beta (, ; uppercase , lowercase , or cursive ; grc, βῆτα, bē̂ta or ell, βήτα, víta) is the second letter of the Greek alphabet. In the system of Greek numerals, it has a value of 2. In Modern Greek, it represents the voiced labiod ...
, the main constituent of senile plaques. BACE1-AS concentrations are elevated in subjects with Alzheimer's disease and in amyloid precursor protein transgenic mice.
miR-96 and hearing loss
Variation within the seed region of mature
miR-96 has been associated with
autosomal dominant
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
, progressive hearing loss in humans and mice. The
homozygous
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism.
Mo ...
mutant mice were profoundly deaf, showing no
cochlea
The cochlea is the part of the inner ear involved in hearing. It is a spiral-shaped cavity in the bony labyrinth, in humans making 2.75 turns around its axis, the modiolus. A core component of the cochlea is the Organ of Corti, the sensory org ...
r responses.
Heterozygous
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism.
Mo ...
mice and humans progressively lose the ability to hear.
Mitochondrial transfer RNAs
A number of mutations within mitochondrial tRNAs have been linked to diseases such as
MELAS syndrome
Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the family of mitochondrial diseases, which also include MIDD (maternally inherited diabetes and deafness, MERRF syndrome, and Leber's hereditary optic neur ...
,
MERRF syndrome
MERRF syndrome (or myoclonic epilepsy with ragged red fibers) is a mitochondrial disease. It is extremely rare, and has varying degrees of expressivity owing to heteroplasmy. MERRF syndrome affects different parts of the body, particularly the mu ...
, and
chronic progressive external ophthalmoplegia
Chronic progressive external ophthalmoplegia (CPEO) is a type of eye disorder characterized by slowly progressive inability to move the eyes and eyebrows. It is often the only feature of mitochondrial disease, in which case the term CPEO may be g ...
.
Distinction between functional RNA (fRNA) and ncRNA
Scientists have started to distinguish ''functional RNA'' (''fRNA'') from ncRNA, to describe regions functional at the RNA level that may or may not be stand-alone RNA transcripts. This implies that fRNA (such as riboswitches,
SECIS element
In biology, the SECIS element (SECIS: ''selenocysteine insertion sequence'') is an RNA element around 60 nucleotides in length that adopts a stem-loop structure. This structural motif (pattern of nucleotides) directs the cell to translate UGA ...
s, and other cis-regulatory regions) is not ncRNA. Yet fRNA could also include
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
, as this is RNA coding for protein, and hence is functional. Additionally
artificially evolved RNAs also fall under the fRNA umbrella term. Some publications
state that ''ncRNA'' and ''fRNA'' are nearly synonymous, however others have pointed out that a large proportion of annotated ncRNAs likely have no function.
It also has been suggested to simply use the term ''RNA'', since the distinction from a protein coding RNA (
messenger RNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the p ...
) is already given by the qualifier ''mRNA''. This eliminates the ambiguity when addressing a gene "encoding a non-coding" RNA. Besides, there may be a number of ncRNAs that are misannoted in published literature and datasets.
See also
*
Extracellular RNA
Extracellular RNA (exRNA) describes RNA species present outside of the cells in which they were transcribed. Carried within extracellular vesicles, lipoproteins, and protein complexes, exRNAs are protected from ubiquitous RNA-degrading enzymes. ...
*
List of RNAs
Ribonucleic acid (RNA) occurs in different forms within organisms and serves many different roles. Listed here are the types of RNA, grouped by role. Abbreviations for the different types of RNA are listed and explained.
By role
RNA ...
*
Nucleic acid structure
Nucleic acid structure refers to the structure of nucleic acids such as DNA and RNA. Chemically speaking, DNA and RNA are very similar. Nucleic acid structure is often divided into four different levels: primary, secondary, tertiary, and quater ...
*
Rfam
Rfam is a database containing information about non-coding RNA (ncRNA) families and other structured RNA elements. It is an annotated, open access database originally developed at the Wellcome Trust Sanger Institute in collaboration with Jane ...
*
Riboswitch
In molecular biology, a riboswitch is a regulatory segment of a messenger RNA molecule that binds a small molecule, resulting in a change in production of the proteins encoded by the mRNA. Thus, an mRNA that contains a riboswitch is directly invo ...
*
Ribozyme
Ribozymes (ribonucleic acid enzymes) are RNA molecules that have the ability to catalyze specific biochemical reactions, including RNA splicing in gene expression, similar to the action of protein enzymes. The 1982 discovery of ribozymes demonst ...
*
RNAs present in environmental samples
A wide variety of non-coding RNAs have been identified in various species of organisms known to science. However, RNAs have also been identified in "metagenomics" sequences derived from samples of DNA or RNA extracted from the environment, which c ...
*
VA (viral associated) RNA
References
External links
Comprehensive database of mammalian ncRNAs(
Wayback Machine
The Wayback Machine is a digital archive of the World Wide Web founded by the Internet Archive, a nonprofit based in San Francisco, California. Created in 1996 and launched to the public in 2001, it allows the user to go "back in time" and see ...
copy)
The Rfam Database— a curated list of hundreds of families of related ncRNAs
NONCODE.org— a free database of all kinds of noncoding RNAs (except tRNAs and rRNAs)
RNAconPrediction and classification of ncRN
BMC Genomics 2014, 15:127ENCODE threads explorer Non-coding RNA characterization.
Nature (journal)
''Nature'' is a British weekly scientific journal founded and based in London, England. As a multidisciplinary publication, ''Nature'' features peer-reviewed research from a variety of academic disciplines, mainly in science and technology. ...
The Non-coding RNA Databases Resource (NRDR)— a curated source of data related to over non-coding RNA databases available over the internet
DASHR- a database of small non-coding RNA
Bioinformatics 2018
{{DEFAULTSORT:Non-Coding Rna
RNA
Molecular genetics