mRNA Untranslated Regions (UTRs)

Flavio Mignone, University of Bari “A. Moro”, Bari, Italy
Graziano Pesole, DISIT – University of Piemonte Orientale, Alessandria, Italy

Published online: January 2018

DOI: 10.1002/9780470015902.a0005009.pub3

Abstract

Eukaryotic messenger ribonucleic acids (mRNAs) possess a tripartite structure that comprises a 5′ untranslated region, a coding region made up of the amino acid coding triplet codons and a 3′ untranslated region. During nuclear maturation of primary transcripts, both ends of mRNA are post‐transcriptionally modified through the addition of a 7‐methyl‐guanosine cap structure at the 5′ end and a polyadenosine tail at the 3′ end. mRNA untranslated regions – UTRs – are involved in the post‐transcriptional regulation of gene expression by modulating the mRNA stability, nucleocytoplasm transport, subcellular localisation and translation efficiency, thus allowing a fine control of the protein product. This regulatory activity is mediated by ‐acting oligonucleotide elements that interact with binding proteins and noncoding RNAs (micro ribonucleic acids – miRNAs and long noncoding ribonucleic acids – lncRNAs) through a combination of primary and secondary structures.

Key Concepts

  • UTRs are involved in the post‐transcriptional regulation of gene expression.
  • UTRs regulate mRNA stability, nucleocytoplasm transport, subcellular localisation and translation efficiency.
  • Alternative splicing can result in mRNAs encoding the same protein under the control of different UTRs.
  • UTRs regulate translation during physiological stress conditions.
  • UTRs are miRNA targets to repress translation or destabilise mRNA.

Keywords: post‐transcriptional regulation; RNA‐binding proteins; translation; mRNA stability; mRNA localisation; miRNA target

Figure 1. Examples of untranslated (UTR) elements with a known secondary structure: (a) human basic fibroblast growth factor (GenBank accession number J04513) IRES element; (b) IRE structure of human transferrin (GenBank accession number M11507); (c) selenocysteine insertion sequence from human SelZ mRNA (GenBank accession number AF166127). Nucleotides that are conserved among the same elements from different transcripts are highlighted by filled circles.
Figure 2. Structure of a eukaryotic mRNA (messenger ribonucleic acid) that depicts some post‐transcriptional regulatory elements. Factors influencing message stability include uAUGs, uORFs, antisense noncoding ribonucleic acids (ncRNAs) and elements embedded in both the 5′ and 3′ UTRs. Modulation of translation may be mediated by the secondary structure of the 5′ UTR, uAUGs or uORFs, as well as by protein‐mediated poly(A) tail interaction with the 7 mG cap. Subcellular localisation of mRNA is often mediated by miRNA elements located in the 3′ UTR.
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References

Andreassi C and Riccio A (2009) To localize or not to localize: mRNA fate is in 3′ UTR ends. Trends in Cell Biology 19 (9): 465–474.

Beaudoin JD and Perreault JP (2013) Exploring mRNA 3′‐UTR G‐quadruplexes: evidence of roles in both alternative polyadenylation and mRNA shortening. Nucleic Acids Research 41 (11): 5898–5911.

Chatterjee S and Pal JK (2009) Role of 5′‐ and 3′‐untranslated regions of mRNAs in human diseases. Biology of the Cell 101 (5): 251–262.

Chekulaeva M and Filipowicz W (2009) Mechanisms of miRNA‐mediated post‐transcriptional regulation in animal cells. Current Opinion in Cell Biology 21 (3): 452–460.

Fabian MR, Sonenberg N and Filipowicz W (2010) Regulation of mRNA translation and stability by microRNAs. Annual Review of Biochemistry 79: 351–379.

Hentze MW, Muckenthaler MU, Galy B and Camaschella C (2010) Two to tango: regulation of mammalian iron metabolism. Cell 142 (1): 24–38.

Hughes MJ and Andrews DW (1997) A single nucleotide is a sufficient 5′ untranslated region for translation in an eukaryotic in vitro system. FEBS Letters 414: 19–22.

Huntzinger E and Izaurralde E (2011) Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nature Reviews Genetics 12 (2): 99–110.

Mercer TR, Dinger ME, Bracken CP, et al. (2010) Regulated post‐transcriptional RNA cleavage diversifies the eukaryotic transcriptome. Genome Research 20 (12): 1639–1650.

Miettinen TP and Björklund M (2015) Modified ribosome profiling reveals high abundance of ribosome protected mRNA fragments derived from 3′ untranslated regions. Nucleic Acids Research 43 (2): 1019–1034.

Mignone F, Gissi C, Liuni S and Pesole G (2002) Untranslated regions of mRNAs. Genome Biology 3 (3): S0004.

Peng SS, Chen CY and Shyu AB (1996) Functional characterization of a non‐AUUUA AU‐rich element from the c‐jun proto‐oncogene mRNA: evidence for a novel class of AU‐rich elements. Molecular and Cellular Biology 16: 1490–1499.

Pesole G, Gissi C, Grillo G, et al. (2000) Analysis of oligonucleotide AUG start codon context in eukaryotic mRNAs. Gene 261: 85–91.

Pesole G, Mignone F, Gissi C, et al. (2001) Structural and functional features of eukaryotic mRNA untranslated regions. Gene 276: 73–81.

Song J, Perreault JP, Topisirovic I and Richard S (2016) RNA G‐quadruplexes and their potential regulatory roles in translation. Translation (Austin) 4 (2): e1244031.

Further Reading

Conne B, Stutz A and Vassalli JD (2000) The 3′ untranslated region of messenger RNA: a molecular ‘hotspot’ for pathology? Nature Medicine 6: 637–641.

Jansen RP (2001) mRNA localization: message on the move. Nature Reviews Molecular Cell Biology 2: 247–256.

Kozak M (1999) Initiation of translation in prokaryotes and eukaryotes. Gene 234: 187–208.

Macdonald P (2001) Diversity in translational regulation. Current Opinion in Cell Biology 13: 326–331.

Mitchell P and Tollervey D (2001) mRNA turnover. Current Opinion in Cell Biology 13: 320–325.

Pesole G, Grillo G, Larizza A and Liuni S (2000) The untranslated regions of eukaryotic mRNAs: structure, function and bioinformatic tools for their analysis. Briefings in Bioinformatics 1: 236–249.

Preiss T and Hentze MW (1999) From factors to mechanisms: translation and translational control in eukaryotes. Current Opinion in Genetics and Development 9: 515–521.

Shyu AB and Wilkinson MF (2000) The double lives of shuttling mRNA binding proteins. Cell 102: 135–138.

van der Velden AW and Thomas AA (1999) The role of the 5′ untranslated region of an mRNA in translation regulation during development. International Journal of Biochemistry and Cell Biology 31: 87–106.

Wilusz CJ, Wormington M and Peltz SW (2001) The cap‐to‐tail guide to mRNA turnover. Nature Reviews Molecular Cell Biology 2: 237–246.

Related Sub-Topics:

Nuclear Magnetic Resonance | Nucleic Acids: Structure, Function, Metabolism | Proteins: Structure, Function, Metabolism | Protein Folding, Evolution and Degradation | Posttranslational Modification | Nucleic Acid Structure | Posttranscriptional Modification | Transcriptional Regulation | Noncoding RNA | Translation and Protein Synthesis | Translational Regulation | RNA Structure and Function | Enzymes: Structure and Action Mechanism
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Article Title: mRNA Untranslated Regions (UTRs)
 
How to Cite close
Mignone, Flavio, and Pesole, Graziano(Jan 2018) mRNA Untranslated Regions (UTRs). In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005009.pub3]