NONSENSE-MEDIATED MESSENGER-RNA DECAY IN YEAST

This chapter describes the mRNA-destabilizing phenomenon as nonsense-mediated mRNA decay, and reviews the cis-acting sequences and trans-acting factors that comprise this pathway in the yeast Saccharomyces cerevisiae. The observation that premature translation termination can promote rapid mRNA decay is just one in a large set of observations that point to an important role for translation in the process of mRNA decay. Additional evidence for this linkage comes from experiments showing that: (1) inhibitors of translation elongation (e.g., cycloheximide) or mutations that inhibit protein synthesis stabilize mRNAs; (2) mRNAs undergoing rapid decay are polysome associated; (3) degradative factors can be polysome associated; (4) instability elements are located in coding regions; (5) the activity of coding-region instability-elements depends on ribosome translocation up to or near the element; and (6) metabolism of the poly(A) tail, a structure involved in translation initiation is a rate-limiting step in the decay of several mRNAs. Although these observations are consistent with the postulated role of ribosomal translocation, the requirement for translation is not likely to be limited to a single step in the turnover process. © 1994, Academic Press Inc.