U1 spliceosomal RNA is the
small nuclear RNA
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 transcribe ...
(snRNA) component of U1
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- ...
(''small nuclear ribonucleoprotein''), an RNA-protein complex that combines with other snRNPs, unmodified
pre-mRNA
A primary transcript is the single-stranded ribonucleic acid (RNA) product synthesized by transcription of DNA, and processed to yield various mature RNA products such as mRNAs, tRNAs, and rRNAs. The primary transcripts designated to be mRNAs a ...
, and various other proteins to assemble a
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 ...
, a large RNA-protein molecular complex upon which
splicing of
pre-mRNA
A primary transcript is the single-stranded ribonucleic acid (RNA) product synthesized by transcription of DNA, and processed to yield various mature RNA products such as mRNAs, tRNAs, and rRNAs. The primary transcripts designated to be mRNAs a ...
occurs. Splicing, or the removal of
introns
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. ...
, is a major aspect of
post-transcriptional modification
Transcriptional modification or co-transcriptional modification is a set of biological processes common to most eukaryotic cells by which an RNA primary transcript is chemically altered following transcription from a gene to produce a mature, func ...
, and takes place only in the
nucleus
Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to:
*Atomic nucleus, the very dense central region of an atom
*Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA
Nucle ...
of
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 ...
.
Structure and function
In humans, the U1 spliceosomal RNA is 164 bases long, forms four stem-loops, and possesses a 5'-trimethylguanosine
five-prime cap
In molecular biology, the five-prime cap (5′ cap) is a specially altered nucleotide on the 5′ end of some primary transcripts such as precursor messenger RNA. This process, known as mRNA capping, is highly regulated and vital in the creation o ...
. Bases 3 to 10 are a conserved sequence that base-pairs with the 5' splice site of
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. ...
s during
RNA splicing
RNA splicing is a process in molecular biology where a newly-made precursor messenger RNA (pre-mRNA) transcript is transformed into a mature messenger RNA (mRNA). It works by removing all the introns (non-coding regions of RNA) and ''splicing'' b ...
, and bases 126 to 133 form the Sm site, around which the Sm ring is assembled. Stem-loop I binds to the
U1-70K protein, stem-loop II binds to the U1 A protein, stem-loops III and IV bind to the core RNP domain, a heteroheptameric Sm ring consisting of SmB/B', SmD1/2/3, SmE, SmF, and SmG. U1 C interacts primarily through protein-protein interactions.
Experimentation has demonstrated that the binding of U1 snRNA to the 5'-splice site is necessary, but not sufficient, to begin spliceosome assembly. Following recruitment of the
U2 snRNP and U5.U4/U6 tri-snRNP the spliceosome transfers the 5'-splice site from the U1 snRNA to
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, a ...
before splicing catalysis occurs.
There are significant differences in sequence and
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 ...
between
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 ...
and
yeast U1 snRNA
U1 is a small nuclear RNA (snRNA) component of the spliceosome and is involved in pre-mRNA splicing.
In the splicing process the 5' end of the U1 snRNA forms complementary base pairing with the 5' splice junction of the intron to be excised, ...
s, the latter being much longer (568
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 ...
s as compared to 164 nucleotides in humans). Nevertheless, secondary structure predictions suggest that all U1 snRNAs share a 'common core' consisting of helices I, II, the proximal region of III, and IV.
This family does not contain the larger yeast sequences.
A non-canonical role for U1 snRNP has recently been described in the regulation of alternative
polyA
Polyadenylation is the addition of a poly(A) tail to an RNA transcript, typically a messenger RNA (mRNA). The poly(A) tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In euka ...
site selection
It is proposed that increased transcription rates "sponge" U1 snRNP, decreasing its availability. This model is supported experimentally, as reducing U1 snRNP levels with
antisense
In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context, ...
morpholino
A Morpholino, also known as a Morpholino oligomer and as a phosphorodiamidate Morpholino oligomer (PMO), is a type of oligomer molecule (colloquially, an oligo) used in molecular biology to modify gene expression. Its molecular structure contains ...
oligonucleotides led to a dose-dependent shift of polyA usage to generate shorter mRNA transcripts.
Role in Disease
U1 snRNP has been implicated in many diseases, especially in those characterized by the presence of misfolded proteins. For instance, a protein component of U1 snRNP called U1-70k from the brain cells of healthy individuals was found to become insoluble in the presence of amyloid aggregates from the brain cells of patients with Alzheimer's disease. U1 overexpression elevates the expression level of
autophagy
Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
and alters lysosomal biogenesis
Similarly in fibroblast cells of patients with a familial form of Amyotrophic Lateral Sclerosis (ALS), the core components of U1 snRNP (namely, the Sm proteins and U1 snRNA) were found to co-mislocalize to the cytoplasm with the mutant version of a protein called FUS (ideally, FUS should localize to the nucleus since it possesses an exposed nuclear localization sequence). The authors of this study also found that experimentally knocking down U1 snRNP, lead to truncations in the axons of motor neurons, suggesting that splicing defects might have a role to play in ALS pathogenesis.
Role in Genome-wide Telescripting
Telescripting is a process by which U1 snRNP suppresses premature cleavage and polyadenylation (PCPA) and allows large transcripts to be synthesized when needed in the cell. Introns possess what are called polyadenylation signals (PAS). These sites are where pre-mRNA can get terminated by cleavage and polyadenylation (a process termed PCPA). In addition to its role in 5' splice site recognition, U1 snRNP protects nascent transcripts by sheltering these exposed PAS in the pre-mRNA such that elongation can continue. Moreover, it has been found that U1 telescripting is particularly important for long-distance transcription elongation in introns of large genes that have a median size of 39 kilo base pairs.
See also
*
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 ...
*
Small nuclear RNA
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 transcribe ...
*
U2 spliceosomal RNA
U2 spliceosomal snRNAs are a species of small nuclear RNA ( snRNA) molecules found in the major spliceosomal (Sm) machinery of virtually all eukaryotic organisms. ''In vivo'', U2 snRNA along with its associated polypeptides assemble to produce the ...
References
Further reading
*
*
External links
*
{{Ribonucleoproteins
Small nuclear RNA
Spliceosome
RNA splicing