title: Exonucleolysis is required for nuclear mRNA quality control in yeast THO mutants.
abstract: Production of aberrant messenger ribonucleoprotein particles (mRNPs) is subject to quality control (QC). In yeast strains carrying mutations of the THO complex, transcription induction triggers a number of interconnected QC phenotypes: (1) rapid degradation of several mRNAs; (2) retention of a fraction of THO-dependent mRNAs in transcription site-associated foci; and (3) formation of a high molecular weight DNA/protein complex in the 3'-ends of THO target genes. Here, we demonstrate that the 3'-5' exonucleolytic domain of the nuclear exosome factor Rrp6p is necessary for establishing all QC phenotypes associated with THO mutations. The N terminus of Rrp6p is also important presumably through its binding to the Rrp6p co-factor Rrp47p. Interestingly, the 3'-5' exonucleolytic activity of Dis3p, the only other active exonuclease of the nuclear exosome, can also contribute to RNA QC in THO mutants, while other nuclear 3'-5' exonucleases cannot. Our data show that exonucleolytic attack by the nuclear exosome is needed both for provoking mRNP QC and for its ensuing elimination of faulty RNA.
authors.affiliation: Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology, The Faculty of Science, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: Jannie
authors.initials: J
authors.lastname: Assenholt
authors.forename: John
authors.initials: J
authors.lastname: Mouaikel
authors.forename: Kasper R
authors.initials: KR
authors.lastname: Andersen
authors.forename: Ditlev E
authors.initials: DE
authors.lastname: Brodersen
authors.forename: Domenico
authors.initials: D
authors.lastname: Libri
authors.forename: Torben Heick
authors.initials: TH
authors.lastname: Jensen
mesh_terms: D004268:DNA-Binding Proteins; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism*; D063326:Exosome Multienzyme Ribonuclease Complex; D005656:Fungal Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C494789:LRP1 protein, S cerevisiae; D009687:Nuclear Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D029701:Saccharomyces cerevisiae Proteins; C026452:messenger ribonucleoprotein; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C542283:DIS3 protein, S cerevisiae; C112610:RRP6 protein, S cerevisiae