Central Dogma of Molecular Biochemistry with Enzymes

molecular genetics Molecular genetics is a branch 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 st ...

, 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 Protein biosynthesis, synthesizing a protein. mRNA is ...

. If it is found on the 5' side, it is called the

5' UTR The 5′ untranslated region (also known as 5′ UTR, leader sequence, transcript leader, or leader RNA) is the region of a messenger RNA (mRNA) that is directly Upstream and downstream (DNA), upstream from the initiation codon. This region is im ...

(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 (biology), translation termination codon. The 3′-UTR often contains regulatory regions that P ...

(or trailer sequence). mRNA is

RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...

that carries information from

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

to the

ribosome Ribosomes () are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (messenger RNA translation). Ribosomes link amino acids together in the order s ...

, the site of protein synthesis (

translation Translation is the communication of the semantics, 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 English la ...

) 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 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. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Dalton (unit), Da or more are called proteins. Chains of fewer t ...

. The 5' UTR is upstream 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 (; less commonly spelled procaryote) is a unicellular organism, single-celled organism whose cell (biology), cell lacks a cell nucleus, nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Gree ...

s and

eukaryote The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

s. The 3' UTR is found immediately following the translation

stop codon In molecular biology, a stop codon (or termination codon) is a codon (nucleotide triplet within messenger RNA) that signals the termination of the translation process of the current protein. Most codons in messenger RNA correspond to the additio ...

. 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 Heredity, heritable traits characteristic of a population over generation ...

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 (genetics), transcription of DNA, and processed to yield various mature RNA products such as mRNAs, tRNAs, and rRNAs. The primary transcript ...

, 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., gen ...

s. The RNA that results from

RNA splicing RNA splicing is a process in molecular biology where a newly-made precursor messenger RNA (pre-mRNA) transcription (biology), transcript is transformed into a mature messenger RNA (Messenger RNA, mRNA). It works by removing all the introns (non-cod ...

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 sequence ...

s. The reason why introns are not considered untranslated regions is that the introns are spliced out in the process of RNA splicing. 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 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 ...

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

s consists of the

Shine–Dalgarno sequence The Shine–Dalgarno (SD) sequence is, sometimes partially, part of a ribosomal binding site in bacterial and archaeal messenger RNA. It is generally located around 8 bases upstream of the start codon AUG. The RNA sequence helps recruit the ribos ...

(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

s is more complex than prokaryotes. It contains a

Kozak consensus sequence The Kozak consensus sequence (Kozak consensus or Kozak sequence) is a Nucleic acid sequence, nucleic acid motif that functions as the protein Translation (biology), translation initiation site in most eukaryotic Messenger RNA, mRNA transcripts. Reg ...

(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 Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...

have been discovered.

Single Nucleotide Polymorphisms In genetics and bioinformatics, 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 ...

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 Childbirth, birth of a baby at fewer than 37 weeks Gestational age (obstetrics), gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 ...

. 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 pres ...

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. We are only beginning to understand the links between proper untranslated region function, and disease states of cells.

References

External links

* * * * {{Cite web , last=((Bio125_Molecular Biology)) , date=Feb 6, 2015 , title=Gene Structure , url=https://www.youtube.com/watch?v=kz4f7vlQFnM , website=YouTube
UTResource
RNA Gene expression