Dataset Information

Rrp6 Moonlights in an RNA Exosome-Independent Manner to Promote Cell Survival and Gene Expression during Stress.

ABSTRACT: The nuclear RNA exosome is essential for RNA processing and degradation. Here, we show that the exosome nuclear-specific subunit Rrp6p promotes cell survival during heat stress through the cell wall integrity (CWI) pathway, independently of its catalytic activity or association with the core exosome. Rrp6p exhibits negative genetic interactions with the Slt2/Mpk1p or Paf1p elongation factors required for expression of CWI genes during stress. Overexpression of Rrp6p or of its catalytically inactive or exosome-independent mutants can partially rescue the growth defect of the mpk1? mutant and stimulates expression of the Mpk1p target gene FKS2. The rrp6? and mpk1? mutants show similarities in deficient expression of CWI genes during heat shock, and overexpression of the CWI gene HSP150 can rescue the stress-induced lethality of the mpk1?rp6? mutant. These results demonstrate that Rrp6p moonlights independently from the exosome to ensure proper expression of CWI genes and to promote cell survival during stress.

SUBMITTER: Wang C

PROVIDER: S-EPMC7587046 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Rrp6 Moonlights in an RNA Exosome-Independent Manner to Promote Cell Survival and Gene Expression during Stress.

Wang Charles C Liu Yanru Y DeMario Samuel M SM Mandric Igor I Gonzalez-Figueroa Carlos C Chanfreau Guillaume F GF

Cell reports 20200601 10

The nuclear RNA exosome is essential for RNA processing and degradation. Here, we show that the exosome nuclear-specific subunit Rrp6p promotes cell survival during heat stress through the cell wall integrity (CWI) pathway, independently of its catalytic activity or association with the core exosome. Rrp6p exhibits negative genetic interactions with the Slt2/Mpk1p or Paf1p elongation factors required for expression of CWI genes during stress. Overexpression of Rrp6p or of its catalytically inact ...[more]

PMID: 32521279

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Project description:The exosome and its nuclear specific subunit Rrp6 form a 3'-5' exonuclease complex that regulates diverse aspects of RNA biology including 3' end processing and degradation of a variety of noncoding RNAs (ncRNAs) and unstable transcripts. Known targets of the nuclear exosome include short (<1000 bp) RNAPII transcripts such as small noncoding RNAs (snRNAs), cryptic unstable transcripts (CUTs), and some stable unannotated transcripts (SUTs) that are terminated by an Nrd1, Nab3, and Sen1 (NNS) dependent mechanism. NNS-dependent termination is coupled to RNA 3' end processing and/or degradation by the Rrp6/exosome in yeast. Recent work suggests Nrd1 is necessary for transcriptome surveillance, regulating promoter directionality and suppressing antisense transcription independently of, or prior to, Rrp6 activity. It remains unclear whether Rrp6 is directly involved in termination; however, Rrp6 has been implicated in the 3' end processing and degradation of ncRNA transcripts including CUTs. To determine the role of Rrp6 in NNS termination globally, we performed RNA sequencing (RNA-Seq) on total RNA and perform ChIP-exo analysis of RNA Polymerase II (RNAPII) localization. Deletion of RRP6 promotes hyper-elongation of multiple NNS-dependent transcripts resulting from both improperly processed 3' RNA ends and faulty transcript termination at specific target genes. The defects in RNAPII termination cause transcriptome-wide changes in mRNA expression through transcription interference and/or antisense repression, similar to previously reported effects of depleting Nrd1 from the nucleus. Elongated transcripts were identified within all classes of known NNS targets with the largest changes in transcription termination occurring at CUTs. Interestingly, the extended transcripts that we have detected in our studies show remarkable similarity to Nrd1-unterminated transcripts at many locations, suggesting that Rrp6 acts with the NNS complex globally to promote transcription termination in addition to 3' end RNA processing and/or degradation at specific targets.

Dataset Information

Rrp6 Moonlights in an RNA Exosome-Independent Manner to Promote Cell Survival and Gene Expression during Stress.

Publications

Rrp6 Moonlights in an RNA Exosome-Independent Manner to Promote Cell Survival and Gene Expression during Stress.

Similar Datasets

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