[CITATION][C] Cytoplasmic regulation of mRNA function: the importance of the 3′ untranslated region

RJ Jackson - Cell, 1993 - Elsevier
RJ Jackson
Cell, 1993Elsevier
Many years ago, it was the prevailing wisdom that neither the control of messenger RNA
(mRNA) translation nor the control of mRNA degradation was important in the overall
regulation of gene expression and that the 3'untranslated region (3'UTR) of an mRNA was
just a boring appendix, without any real functional significance. How totally wrong were
these ancient prejudices was amply revealed at the CNRS Jacques Monod Conference on
Cytoplasmic Aspects of the Post-Transcriptional Regulation of Gene Expression, organized …
Many years ago, it was the prevailing wisdom that neither the control of messenger RNA (mRNA) translation nor the control of mRNA degradation was important in the overall regulation of gene expression and that the 3’untranslated region (3’UTR) of an mRNA was just a boring appendix, without any real functional significance. How totally wrong were these ancient prejudices was amply revealed at the CNRS Jacques Monod Conference on Cytoplasmic Aspects of the Post-Transcriptional Regulation of Gene Expression, organized by HB Osborne and MF Tuite and held at La Londe-les-Maures, France, March 28th-April 2nd. The meeting covered an unusually wide range of topics pertinent to mRNA function, principally with respect to eukaryotes, but with useful exercises in lateral thinking provided by sessions on prokaryotes. Because of the very breadth of coverage, it is impossible to do justice here to all the various topics discussed, and what follows is an account of the more closely interrelated topics. The most significant single take-home message was the overriding importance of the 3’UTR of eukaryotic mRNA as the repository of all signals determining mRNA localization, of almost all signals (with one possible exception) controlling polyadenylation, of many motifs regulating mRNA stability (most of the other known signals being in the coding region), and of signals controlling translation initiation, particularly for translationally regulated mRNAs in germline cells. Other unexpected functions associated with the 3’UTR have been reported recently, such as the control of growth and differentiation of myoblasts (Rastinejad and Blau, 1993) and mutations responsible for myotonic dystrophy (Brook et al., 1992).
Control of Translation Initiation by Modulation of Initiation Factor Activity Control of initiation by phosphorylation of initiation factor elF-2 received less attention than at previous meetings, apart from the very influential work on the control of yeast GCN4 mRNA translation by amino acid starvation. Whereas phosphorylation of elF-2, which catalyzes the binding of initiator Met-tRNA to 40s ribosomal subunits, leads to reduced translation of typical mRNAs (Jackson, 1991) it actually causes an increase in GCN4 mRNA translation as a consequence of the disposition of four small reading frames in the5’UTR. It would be intriguing to know whether elF-2 phosphorylation could similarly promote increased translation of those mammalian mRNAs with multiple small reading frames in the 5’UTR, mRNAs that include many proto-oncogene, transcription factor, and lymphokine mRNAs (Kozak, 1991). Upon amino acid starvation of yeast, the increase in deacylated tRNA concentration triggers the activity of the
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