A specific role for the C-terminal region of the Poly(A)-binding protein in mRNA decay.
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.
Simón
Ernesto
E
Equipe Labellisée La Ligue, Centre de Génétique Moléculaire, CNRS UPR2167 associée à l'Université P. et M. Curie, Avenue de la Terrasse, 91198 Gif sur Yvette, France.
Séraphin
Bertrand
B
D018389:Codon, Nonsense; D004722:Endoribonucleases / Q000235:genetics; D011061:Poly A / Q000378:metabolism; D039102:Poly(A)-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D039381:RNA Cap-Binding Proteins; D020871:RNA Stability; D034443:RNA Transport; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion
D018389:Codon, Nonsense; D039102:Poly(A)-Binding Proteins; D039381:RNA Cap-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C450100:pab1 protein, S cerevisiae; D011061:Poly A; C078657:CCR4 protein, S cerevisiae; C100868:DCP1 protein, S cerevisiae; D004722:Endoribonucleases; D012260:Ribonucleases; C079009:POP2 protein, S cerevisiae