Regulation of the Ysh1 Endonuclease of the MRNA Cleavage/polyadenylation Complex by Ubiquitin-mediated Degradation

Overview

Journal RNA Biol

Specialty Molecular Biology

Date 2020 Feb 4

PMID 32009536

Citations 8

Authors

Susan D Lee

Hui-Yun Liu

Joel H Graber

Daniel Heller-Trulli

Katarzyna Kaczmarek Michaels

Juan Francisco Cerezo

Claire L Moore

Affiliations

Soon will be listed here.

Abstract

Mutation of the essential yeast protein Ipa1 has previously been demonstrated to cause defects in pre-mRNA 3' end processing and growth, but the mechanism underlying these defects was not clear. In this study, we show that the mutation causes a striking depletion of Ysh1, the evolutionarily conserved endonuclease subunit of the 19-subunit mRNA Cleavage/Polyadenylation (C/P) complex, but does not decrease other C/P subunits. overexpression rescues both the growth and 3' end processing defects of the mutant. mRNA level is unchanged in cells, and proteasome inactivation prevents Ysh1 loss and causes accumulation of ubiquitinated Ysh1. Ysh1 ubiquitination is mediated by the Ubc4 ubiquitin-conjugating enzyme and Mpe1, which in addition to its function in C/P, is also a RING ubiquitin ligase. In summary, Ipa1 affects mRNA processing by controlling the availability of the C/P endonuclease and may represent a regulatory mechanism that could be rapidly deployed to facilitate reprogramming of cellular responses.

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