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PMID: 16260613 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A nuclear surveillance pathway for mRNAs with defective polyadenylation.

Molecular and cellular biology ·Vol. 25 ·No. 22 ·2005-11-00 ·Pages 9996-10004

Milligan L, Torchet C, Allmang C, Shipman T, Tollervey D

Abstract

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.

MeSH Terms
Catalysis Cell Nucleus/metabolism DEAD-box RNA Helicases Exonucleases/metabolism Exoribonucleases/metabolism,physiology Exosome Multienzyme Ribonuclease Complex Gene Expression Regulation, Fungal Glucose/pharmacology Kluyveromyces/metabolism Models, Biological Models, Genetic Mutation Nuclear Proteins/metabolism Pancreatitis-Associated Proteins Phenotype Poly A Polyadenylation Polynucleotide Adenylyltransferase/chemistry RNA/chemistry RNA Helicases/metabolism RNA, Messenger/chemistry,metabolism Saccharomyces cerevisiae/metabolism Saccharomyces cerevisiae Proteins/metabolism,physiology Temperature Time Factors
Chemicals
Nuclear Proteins Pancreatitis-Associated Proteins REG3A protein, human RNA, Messenger SKI6 protein, S cerevisiae Saccharomyces cerevisiae Proteins Poly A RNA Polynucleotide Adenylyltransferase Exonucleases Exoribonucleases Exosome Multienzyme Ribonuclease Complex MTR3 protein, S cerevisiae RRP6 protein, S cerevisiae MTR4 protein, S cerevisiae DEAD-box RNA Helicases RNA Helicases Glucose
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Milligan Laura
Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom.
Torchet Claire
Allmang Christine
Shipman Tracey
Tollervey David
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
2005-11-00
Pages
9996-10004
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1280253
Subset
IM
Grants
Wellcome Trust · United Kingdom
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