Abstract
The nuclear RNA exosome plays a key role in controlling the levels of multiple protein-coding and non-coding RNAs. Recruitment of the exosome to specific RNA substrates is mediated by RNA-binding co-factors. The transient interaction between co-factors and the exosome as well as the rapid decay of RNA substrates make identification of exosome co-factors challenging. Here, we use comparative poly(A)+ RNA interactome capture in fission yeast expressing three different mutants of the exosome to identify proteins that interact with poly(A)+ RNA in an exosome-dependent manner. Our analyses identify multiple RNA-binding proteins whose association with RNA is altered in exosome mutants, including the zinc-finger protein Mub1. Mub1 is required to maintain the levels of a subset of exosome RNA substrates including mRNAs encoding for stress-responsive proteins. Removal of the zinc-finger domain leads to loss of RNA suppression under non-stressed conditions, altered expression of heat shock genes in response to stress, and reduced growth at elevated temperature. These findings highlight the importance of exosome-dependent mRNA degradation in buffering gene expression networks to mediate cellular adaptation to stress.
Highlights
Regulation of RNA maturation and degradation is crucial to accurate gene expression (Kilchert et al, 2016)
We focus on the uncharacterised zf-MYND (MYeloid, Nervy, and DEAF-1)-type zinc-finger protein Mub1, which is highly enriched on poly(A)+ RNA in the exosome mutants
The underlying hypothesis behind this approach was that stabilisation of RNAs targeted by the exosome would facilitate the capture of proteins that are functionally linked to the exosome, which are likely to be enriched on these RNAs (Fig 1B)
Summary
Regulation of RNA maturation and degradation is crucial to accurate gene expression (Kilchert et al, 2016). The nucleolytic RNA exosome complex is involved in the biogenesis of multiple types of transcripts produced by RNA polymerases I, II, and III (Pol I, II, and III) (Mitchell et al, 1997; Allmang et al, 1999; Isken & Maquat, 2007; Kiss & Andrulis, 2010; Gudipati et al, 2012; Schneider et al, 2012a; Chlebowski et al, 2013; Szczepinska et al, 2015). Mutations in the nuclear exosome lead to severe neurodegenerative diseases in humans, such as spinal muscular atrophy and pontocerebellar hypoplasia (Wan et al, 2012; Boczonadi et al, 2014; Yang et al, 2020)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
