Poster abstracts

Poster number 39 submitted by Xiaoqiang Liu

Hsp90 control of mRNA decay through stabilization of the PMR1 mRNA endonuclease

Yong Peng (Department of Molecular and Cellular Biochemistry; The Ohio State University; Columbia University), Xiaoqiang Liu (Department of Molecular and Cellular Biochemistry; The Ohio State University), Daniel R. Schoenberg (Department of Molecular and Cellular Biochemistry; The Ohio State University)

Abstract:
The PMR1 mRNA endonuclease forms a selective complex with its translating
substrate mRNAs where it is activated to initiate mRNA decay. Previous work showed
tyrosine phosphorylation is required for PMR1 targeting to this polysome-bound
complex, and identified c-Src as the responsible kinase. c-Src phosphorylation occurs in
a distinct complex, and the current study identifies Hsp90 as a critical member of this.
Hsp90 binds to the central domain of PMR1 and its binding is inhibited by geldanamycin.
Geldanamycin stabilizes substrate mRNA to PMR1-mediated decay and causes the
mRNA endonuclease to rapidly disappear. We show that PMR1 is inherently unstable,
that it is degraded by the 26S proteasome, and that geldanamycin activates a pre-existing
decay process. Lastly, we show that PMR1 is ubiquitinated, its ubiquitination is
stimulated by geldanamycin, and this activates its degradation. c-Src is regulated
similarly by Hsp90, and results of this study identify a new process controlling mRNA
decay through changes in effector protein stability.

Keywords: PMR1, endonuclease-mediated mRNA decay, Hsp90