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

Adrien Birot, Krzysztof Kus, Emily Priest, Ahmad Al Alwash, Alfredo Castello, Shabaz Mohammed, Lidia Vasiljeva, Cornelia Kilchert

Life science alliance 2022 Feb

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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. © 2021 Birot et al.

Citation

Adrien Birot, Krzysztof Kus, Emily Priest, Ahmad Al Alwash, Alfredo Castello, Shabaz Mohammed, Lidia Vasiljeva, Cornelia Kilchert. RNA-binding protein Mub1 and the nuclear RNA exosome act to fine-tune environmental stress response. Life science alliance. 2022 Feb;5(2)