RNA-binding protein Mub1 and the nuclear RNA exosome act to fine-tune environmental stress response

Birot, A., Kus, K., Priest, E., Al Alwash, A., Castello, A. , Mohammed, S., Vasiljeva, L. and Kilchert, C. (2022) RNA-binding protein Mub1 and the nuclear RNA exosome act to fine-tune environmental stress response. Life Science Alliance, 5(2), e202101111. (doi: 10.26508/lsa.202101111) (PMID:34848435) (PMCID:PMC8645331)

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.

• Item Type: Articles
• Additional Information: This work was supported by a Wellcome Trust Senior Research fellowship to L Vasiljeva (WT106994/Z/15/Z), and the Emmy Noether Programme of the Deutsche Forschungsgemeinschaft (DFG) to C Kilchert (KI 1657/2-1). We acknowledge the Micron Advanced Bioimaging Unit (supported by the Wellcome Strategic Awards 091911/B/10/Z and 107457/Z/15/Z) for their support and assistance in performing the FISH experiments.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Castello, Professor Alfredo

Creator Roles

Castello, A.: Methodology, Writing – review and editing

• Authors: Birot, A., Kus, K., Priest, E., Al Alwash, A., Castello, A., Mohammed, S., Vasiljeva, L., and Kilchert, C.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Life Science Alliance
• Publisher: Life Science Alliance
• ISSN: 2575-1077
• ISSN (Online): 2575-1077
• Published Online: 30 November 2021
• Copyright Holders: Copyright © 2021 Birot et al.
• First Published: First published in Life Science Alliance 5(2): e202101111
• Publisher Policy: Reproduced under a Creative Commons License