Equipe Labellisee La Ligue, Centre de Genetique Moleculaire, CNRS UPR2167 associee a l'Universite P- et M- Curie, Avenue de la Terrasse, 91198 Gif sur Yvette, France-
Abstract: mRNA poly-A- tails affect translation, mRNA export and mRNA stability, with translation initiation involving a direct interaction between eIF4G and the poly-A--binding protein Pab1- The latter factor contains four RNA recognition motifs followed by a C-terminal region composed of a linker and a PABC domain- We show here that yeast mutants lacking the C-terminal domains of Pab1 display specific synthetic interactions with mutants in the 5'-3' mRNA decay pathway- Moreover, these mutations impair mRNA decay in vivo without significantly affecting mRNA export or translation- Inhibition of mRNA decay occurs through slowed deadenylation- In vitro analyses demonstrate that removal of the Pab1 linker domain directly interferes with the ability of the Pop2-Ccr4 complex to deadenylate the Pab1-bound poly-A-- Binding assays demonstrate that this results from a modulation of poly-A- packaging by the Pab1 linker region- Overall, our results demonstrate a direct involvement of Pab1 in mRNA decay and reveal the modular nature of this factor, with different domains affecting various cellular processes- These data suggest new models involving the modulation of poly-A- packaging by Pab1 to control mRNA decay-