28 Interaction of mRNA Translation and mRNA Degradation in Saccharomyces cerevisiae

Abstract

BIOLOGICAL SIGNIFICANCE OF mRNA TURNOVER It has become clear that mRNA turnover can play a major role in the control of gene expression. In eukaryotic cells, the decay rates of individual mRNAs vary by more than two orders of magnitude (Singer and Penman 1973; Spradling et al. 1975; Cabrera et al. 1984). There have also been a growing number of examples wherein the regulation of gene expression in response to an environmental cue is attained by altering the rates of degradation for specific mRNAs (for review, see Ross 1995). In addition, a specialized system of mRNA decay, referred to as mRNA surveillance, functions to ensure that mRNA biogenesis has been completed correctly by degrading aberrant transcripts (for reviews, see Chapters 29 and 30). Finally, specific mechanisms of mRNA degradation function in the genespecific silencing induced by double-stranded RNA (for review, see Fire 1999). The numerous and diverse roles for mRNA degradation suggest that the modulation of mRNA stability is a critical step in the regulation of eukaryotic gene expression. PATHWAYS OF mRNA DEGRADATION Four distinct pathways of mRNA turnover have been identified in eukaryotic organisms (Fig. 1). In yeast, degradation begins by shortening of the 3′ poly(A) tail followed by removal of the 5′ cap structure (decapping), thus allowing 5′ to 3′ exonucleolytic digestion of the body of the transcript (Muhlrad and Parker 1992; Decker and Parker 1993; Hsu and Stevens 1993; Muhlrad et al. 1994, 1995). Alternatively, mRNAs can be degraded 3′ to 5′ following deadenylation (Muhlrad et al....