Comparative poly(A)+ RNA interactome capture of fission yeast RNA exosome mutants reveals insights into RNA biogenesis

Abstract

The nuclear RNA exosome plays a key role in mediating degradation and processing of multiple cellular RNAs. Recognition of the specific RNA substrates by the exosome is mediated by the RNA-binding co-factors. Transient binding of co-factors either to the exosome or the substrate RNAs as well as their rapid decay make identification of the co-factors challenging. Here, we employ a comparative poly(A)+ RNA interactome capture approach in the fission yeast exosome mutants to identify proteins that interact with poly(A)+ RNA in an exosome-dependent manner. Our analyses identified multiple proteins whose occupancy on RNA is altered in the exosome mutants including zinc-finger protein Mub1. Mub1 is required to maintain the levels of a subset of the 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 importance of exosome-dependent mRNA degradation in buffering gene expression networks to mediate cellular adaptation to stress.