4.8 Article

Nrd1p identifies aberrant and natural exosomal target messages during the nuclear mRNA surveillance in Saccharomyces cerevisiae

期刊

NUCLEIC ACIDS RESEARCH
卷 49, 期 20, 页码 11512-11536

出版社

OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab930

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资金

  1. DBT [BT/PR27917/BRB/10/1673/2018]
  2. Jadavpur University [RUSA 2.0 Research Grant]
  3. Government of West Bengal
  4. CSIR [38(1427)/16/EMR-II]

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The Nrd1p-Nab3p-Sen1p (NNS) complex plays a universal role in nuclear decay of all categories of aberrant mRNAs in yeast, with the interaction domain of Nrd1p and RNA Pol II being crucial for its function.
Nuclear degradation of aberrant mRNAs in Saccharomyces cerevisiae is accomplished by the nuclear exosome and its cofactors TRAMP/CTEXT. Evidence from this investigation establishes a universal role of the Nrd1p-Nab3p-Sen1p (NNS) complex in the nuclear decay of all categories of aberrant mRNAs. In agreement with this, both nrd1-1 and nrd1-2 mutations impaired the decay of all classes of aberrant messages. This phenotype is similar to that displayed by GAL::RRP41 and rrp6-Delta mutant yeast strains. Remarkably, however, nrd1 Delta(C)(ID) mutation (lacking the C-terminal domain required for interaction of Nrd1p with RNAPII) only diminished the decay of aberrant messages with defects occurring during the early stage of mRNP biogenesis, without affecting other messages with defects generated later in the process. Co-transcriptional recruitment of Nrd1p on the aberrant mRNAs was vital for their concomitant decay. Strikingly, this recruitment on to mRNAs defective in the early phases of biogenesis is solely dependent upon RNAPII. In contrast, Nrd1p recruitment onto export-defective transcripts with defects occurring in the later stage of biogenesis is independent of RNAPII and dependent on the CF1A component, Pcf11p, which explains the observed characteristic phenotype of nrd1 Delta(C)(ID) mutation. Consistently, pcf11-2 mutation displayed a selective impairment in the degradation of only the export-defective messages.

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