5′‐UTRs and Regulation

The 5¢ untranslated region consists of the leading part of a cellular messenger ribonucleic acid (mRNA) from the 5¢ end to the translation start codon AUG. Precursor mRNA is posttranscriptionally modified by the removal of introns and by the addition at the 5¢ end of a 7-methyl-guanylate cap structure, which has a crucial role in translation initiation and in regulating transcript stability. 5¢-UTRs as well as 3¢-UTRs, are deeply involved in regulation of gene expression through specific motifs that can affect mRNA stability, subcellular localization, nuclear export, tissue specificity and efficiency of translation.

Keywords: translation initiation; mRNA stability; uAUG; uORF; internal ribosome entry site

Figure 1. mRNAs with alternative 5¢-UTRs can be generated either by the use of alternative promoters, which results in different transcription start sites (TSS1 and TSS2), or by alternative spicing events. In this way, alternative 5¢-UTRs corresponding to the same gene may contain different combinations of regulatory elements, as shown here. CDS: coding sequence; mG7: 7-methyl-guanylate; IRES: internal ribosome entry site; sAUG: start AUG; uAUG: upstream AUG; uORF: upstream open reading frame.
Figure 2. Translation initiation regulation. (a) Canonical scanning model; (b) ribosome stalling; (c) inefficient (top) and efficient (bottom) reinitiation, depending on the distance between the uORF and the sAUG; (d) regulation by uORF-encoded peptide; (e) detachment of the ribosome mediated by an uORF stop codon; (f) IRES-mediated initiation; (g) inhibition of secondary structure; (h) in-frame or out-of-frame translation starting from an uAUG.
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 References
    Chung BY, Simons C, Firth AE, Brown CM and Hellens RP (2006) Effect of 5¢ UTR introns on gene expression in Arabidopsis thaliana. BMC Genomics 7: 120.
    Hu MC, Tranque P, Edelman GM and Mauro VP (1999) rRNA-complementarity in the 5¢ untranslated region of mRNA specifying the Gtx homeodomain protein: evidence that base-pairing to 18S rRNA affects translational efficiency. Proceedings of the National Academy of Sciences of the USA 96: 1339–1344.
    Iacono M, Mignone F and Pesole G (2005) uAUG and uORFs in human and rodent 5¢ untranslated mRNAs. Gene 349: 97–105.
    Kochetov AV, Ischenko IV, Vorobiev DG et al. (1998) Eukaryotic mRNAs encoding abundant and scarce proteins are statistically dissimilar in many structural features. FEBS Letters 440(3): 351–355.
    Ledda M, Di Croce M, Bedini B et al. (2005) Effect of 3¢UTR length on the translational regulation of 5¢-terminal oligopyrimidine mRNAs. Gene 344: 213–220.
    Lopez-Lastra M, Rivas A and Barria MI (2005) Protein synthesis in eukaryotes: the growing biological relevance of cap-independent translation initiation. Biological Research 38: 121–146.
    Mignone F, Gissi C, Liuni S and Pesole G (2002) Untranslated regions of mRNAs. Genome Biology 3: 0004.1–0004.10.
    Mignone F and Pesole G (2002) rRNA-like sequences in human mRNAs. Applied Bioinformatics 1(3): 145–154.
    Pendleton LC, Goodwin BL, Solomonson LP and Eichler DC (2005) Regulation of endothelial argininosuccinate synthase expression and NO production by an upstream open reading frame. Journal of Biological Chemistry 280(25): 24252–24260.
    Shantz LM and Pegg AE (1999) Translational regulation of ornithine decarboxylase and other enzymes of the polyamine pathway. International Journal of Biochemistry and Cell Biology 31: 107–122.
    Svitkin YV, Pause A, Haghighat A et al. (2001) The requirement for eukaryotic initiation factor 4A (eIF4A) in translation is in direct proportion to the degree of mRNA 5¢ secondary structure. RNA 7(3): 382–394.
    Tanguay RL and Gallie DR (1996) Translational efficiency is regulated by the length of the 3¢ untranslated region. Molecular and Cellular Biology 16(1): 146–156.
 Further Reading
    Hellen CU and Sarnow P (2001) Internal ribosome entry sites in eukaryotic mRNA molecules. Genes and Development 15: 1593–1612.
    Kozak M (1999) Initiation of translation in prokaryotes and eukaryotes. Gene 234: 187–208.
    Meijer HA and Thomas AA (2002) Control of eukaryotic protein synthesis by upstream open reading frames in the 5¢-untranslated region of an mRNA. Biochemical Journal 367: 1–11.
    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.
    Vilela C, Ramirez CV, Linz B, Rodrigues-Pousada C and McCarthy JE (1999) Post-termination ribosome interactions with the 5¢ UTR modulate yeast mRNA stability. EMBO Journal 18: 3139–3152.
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Mignone, Flavio, and Pesole, Graziano(Sep 2007) 5′‐UTRs and Regulation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005010.pub2]