MULTIPLE FUNCTIONS FOR POLY(A)-BINDING PROTEIN IN MESSENGER-RNA DECAPPING AND DEADENYLATION IN YEAST

The first step in the decay of many eukaryotic mRNAs is shortening of the poly(A) tail. In yeast, deadenylation leads to mRNA decapping and subsequent 5' --> 3' exonucleolytic degradation of the transcript body . We have determined that the major poly(A)-binding protein Pab1p play s at least two critical roles in this pathway. first, mRNAs in pab1 De lta strains were decapped prior to deadenylation. This observation def ines a new function for Pab1p as an inhibitor of mRNA decapping. Moreo ver, mutations that inhibit mRNA turnover suppress the inviability of a pab1 Delta mutation, suggesting that premature mRNA decapping in pab 1 Delta strains contributes to cell death. Second, we find that Pab1p is not required for deadenylation, although in its absence poly(A) tai l shortening rates are significantly reduced. In addition, in the abse nce of Pab1p, newly synthesized mRNAs had poly(A) tails longer than th ose in wild-type strains and showed an unexpected temporal delay prior to the initiation of deadenylation and degradation. These results def ine new and critical functions for Pab1p in the regulation of mRNA dec apping and deadenylation, two important control points in the specific ation of mRNA half-lives. Moreover, these results suggest that Pab1p f unctions in additional phases of mRNA metabolism such as mRNP maturati on.