Untranslated Regions
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In
molecular genetics Molecular genetics is a sub-field of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the ...
, an untranslated region (or UTR) refers to either of two sections, one on each side of a coding sequence on a strand of
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 synthesizing a protein. mRNA is created during the ...
. If it is found on the 5' side, it is called the 5' UTR (or leader sequence), or if it is found on the 3' side, it is called the
3' UTR In molecular genetics, the three prime untranslated region (3′-UTR) is the section of messenger RNA (mRNA) that immediately follows the translation termination codon. The 3′-UTR often contains regulatory regions that post-transcriptionall ...
(or trailer sequence). mRNA is RNA that carries information from DNA to the ribosome, the site of protein synthesis (
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 ...
) within a cell. The mRNA is initially transcribed from the corresponding DNA sequence and then translated into protein. However, several regions of the mRNA are usually not translated into protein, including the 5' and 3' UTRs. Although they are called untranslated regions, and do not form the
protein-coding The coding region of a gene, also known as the coding sequence (CDS), is the portion of a gene's DNA or RNA that codes for protein. Studying the length, composition, regulation, splicing, structures, and functions of coding regions compared to no ...
region of the gene, uORFs located within the 5' UTR can be translated into
peptides 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. ...
. The 5' UTR is
upstream Upstream may refer to: * Upstream (bioprocess) * ''Upstream'' (film), a 1927 film by John Ford * Upstream (networking) * ''Upstream'' (newspaper), a newspaper covering the oil and gas industry * Upstream (petroleum industry) * Upstream (software ...
from the coding sequence. Within the 5' UTR is a sequence that is recognized by the ribosome which allows the ribosome to bind and initiate translation. The mechanism of translation initiation differs 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 & Con ...
s and
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. Bact ...
s. The 3' UTR is found immediately following the translation stop codon. The 3' UTR plays a critical role in translation termination as well as
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, f ...
. These often long sequences were once thought to be useless or junk mRNA that has simply accumulated over evolutionary time. However, it is now known that the untranslated region of mRNA is involved in many regulatory aspects of gene expression in eukaryotic organisms. The importance of these non-coding regions is supported by evolutionary reasoning, as
natural selection Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the heritable traits characteristic of a population over generations. Cha ...
would have otherwise eliminated this unusable RNA. It is important to distinguish the 5' and 3' UTRs from other non-protein-coding RNA. Within the coding sequence 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 ...
, there can be found sections of RNA that will not be included in the protein product. These sections of RNA are called
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. The RNA that results from RNA splicing is a sequence of
exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequenc ...
s. The reason why introns are not considered untranslated regions is that the introns are spliced out in the process of
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 ...
. The introns are not included in the
mature mRNA Mature messenger RNA, often abbreviated as mature mRNA is a eukaryotic RNA transcript that has been spliced and processed and is ready for translation in the course of protein synthesis. Unlike the eukaryotic RNA immediately after transcription ...
molecule that will undergo translation and are thus considered non-protein-coding RNA.


History

The untranslated regions of mRNA became a subject of study as early as the late 1970s, after the first mRNA molecule was fully sequenced. In 1978, the 5' UTR of the human gamma-globin mRNA was fully sequenced. In 1980, a study was conducted on the 3' UTR of the duplicated human alpha-globin genes.


Evolution

The untranslated region is seen in prokaryotes and eukaryotes, although the length and composition may vary. In prokaryotes, the 5' UTR is typically between 3 and 10 nucleotides long. In eukaryotes, the 5' UTR can be hundreds to thousands of nucleotides long. This is consistent with the higher complexity of the genomes of eukaryotes compared to prokaryotes. The 3' UTR varies in length as well. The poly-A tail is essential for keeping the mRNA from being degraded. Although there is variation in lengths of both the 5' and 3' UTR, it has been seen that the 5' UTR length is more highly conserved in evolution than the 3' UTR length.


Prokaryotes

The 5' UTR of Prokaryotes consists of the Shine-Dalgarno sequence (5'-AGGAGGU-3'). This sequence is found 3-10 base pairs upstream from the initiation codon. The initiation codon is the start site of translation into protein.


Eukaryotes

The 5' UTR of Eukaryotes is more complex than prokaryotes. It contains a Kozak consensus sequence (ACCAUGG). This sequence contains the initiation codon. The initiation codon is the start site of translation into protein.


Links to disease

The importance of these untranslated regions of mRNA is just beginning to be understood. Various medical studies are being conducted that have found connections between mutations in untranslated regions and increased risk for developing a particular disease, such as cancer. For example, associations between polymorphisms in the HLA-G 3′UTR region and development of colorectal cancer have been discovered.
Single Nucleotide Polymorphisms In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...
in the 3' UTR of another gene have also been associated with susceptibility to
preterm birth Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is betwee ...
. Mutations in the 3' UTR of the APP gene are related to development of
cerebral amyloid angiopathy Cerebral amyloid angiopathy (CAA) is a form of angiopathy in which amyloid beta peptide deposits in the walls of small to medium blood vessels of the central nervous system and meninges. The term ''congophilic'' is sometimes used because the p ...
.


Further study

Through the recent study of untranslated regions, general information has been gathered about the nature and function of these elements. However, there is still much that is unknown about these regions of mRNA. Since the regulation of gene expression is critical in the proper function of cells, this is an area of study that needs to be investigated further. It is important to consider that mutations in 3' untranslated regions have the potential to alter the expression of several genes that may appear unrelated.{{Cite journal, last1=Chatterjee, first1=Sangeeta, last2=Pal, first2=Jayanta K., date=2009-05-01, title=Role of 5′- and 3′-untranslated regions of mRNAs in human diseases, journal=Biology of the Cell, language=en, volume=101, issue=5, pages=251–262, doi=10.1042/BC20080104, pmid=19275763, s2cid=22689654, issn=1768-322X, doi-access=free We are only beginning to understand the links between proper untranslated region function, and disease states of cells.


See also

*
Atlas of UTR Regulatory Activity The Atlas of UTR Regulatory Activity (AURA), a biological database, now at its second version, is a manually curated and comprehensive catalog of human 5' and 3' untranslated sequences (UTR) and UTR regulatory annotations. It includes basic annot ...
*
Coding region The coding region of a gene, also known as the coding sequence (CDS), is the portion of a gene's DNA or RNA that codes for protein. Studying the length, composition, regulation, splicing, structures, and functions of coding regions compared to no ...
* Five prime untranslated region * History of RNA biology *
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. miR ...
*
Three prime untranslated region In molecular genetics, the three prime untranslated region (3′-UTR) is the section of messenger RNA (mRNA) that immediately follows the translation termination codon. The 3′-UTR often contains regulatory regions that post-transcriptionall ...
* Upstream open reading frames (uORFs)


References


External links

* http://highered.mheducation.com/sites/0072507470/student_view0/chapter3/animation__mrna_synthesis__transcription___quiz_1_.html * http://highered.mheducation.com/sites/0072507470/student_view0/chapter3/animation__how_translation_works.html * http://utrsite.ba.itb.cnr.it/index.php/default/ * https://www.youtube.com/watch?v=kz4f7vlQFnM
UTResource
RNA Gene expression