A nuclear surveillance pathway for mRNAs with defective polyadenylation.
The pap1-5 mutation in poly(A) polymerase causes rapid depletion of mRNAs at restrictive temperatures. Residual mRNAs are polyadenylated, indicating that Pap1-5p retains at least partial activity. In pap1-5 strains lacking Rrp6p, a nucleus-specific component of the exosome complex of 3'-5' exonucleases, accumulation of poly(A)+ mRNA was largely restored and growth was improved. The catalytically inactive mutant Rrp6-1p did not increase growth of the pap1-5 strain and conferred much less mRNA stabilization than rrp6delta. This may indicate that the major function of Rrp6p is in RNA surveillance. Inactivation of core exosome components, Rrp41p and Mtr3p, or the nuclear RNA helicase Mtr4p gave different phenotypes, with accumulation of deadenylated and 3'-truncated mRNAs. We speculate that slowed mRNA polyadenylation in the pap1-5 strain is detected by a surveillance activity of Rrp6p, triggering rapid deadenylation and exosome-mediated degradation. In wild-type strains, assembly of the cleavage and polyadenylation complex might be suboptimal at cryptic polyadenylation sites, causing slowed polyadenylation.
Milligan
Laura
L
Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom.
Torchet
Claire
C
Allmang
Christine
C
Shipman
Tracey
T
Tollervey
David
D
D002384:Catalysis; D002467:Cell Nucleus / Q000378:metabolism*; D053487:DEAD-box RNA Helicases; D005092:Exonucleases / Q000378:metabolism; D005095:Exoribonucleases / Q000378:metabolism / Q000502:physiology*; D063326:Exosome Multienzyme Ribonuclease Complex; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000494:pharmacology; D007716:Kluyveromyces / Q000378:metabolism; D008954:Models, Biological; D008957:Models, Genetic; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D000073718:Pancreatitis-Associated Proteins; D010641:Phenotype; D011061:Poly A; D026723:Polyadenylation; D011062:Polynucleotide Adenylyltransferase / Q000737:chemistry*; D012313:RNA / Q000737:chemistry; D020365:RNA Helicases / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D013696:Temperature; D013997:Time Factors
D009687:Nuclear Proteins; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D012333:RNA, Messenger; C111978:SKI6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D011061:Poly A; D012313:RNA; D011062:Polynucleotide Adenylyltransferase; D005092:Exonucleases; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C097433:MTR3 protein, S cerevisiae; C112610:RRP6 protein, S cerevisiae; C101004:MTR4 protein, S cerevisiae; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases; D005947:Glucose