Endonuclease-mediated mRNA decay requires tyrosine phosphorylation of polysomal ribonuclease 1 (PMR1) for the targeting and degradation of polyribosome-bound substrate mRNA.

The Journal of Biological Chemistry
Feng YangD R Schoenberg

Abstract

PMR1 is an endonuclease that is activated by estrogen to degrade Xenopus albumin mRNA. A previous report showed that the functional unit of endonuclease-mediated mRNA decay is a approximately 680-kDa polysome-bound complex that contains both PMR1 and substrate mRNA. PMR1 contains two domains involved in endonuclease targeting to polysomes, an N-terminal domain that lies between residues 200 and 250, and a C-terminal domain that lies within the last 100 residues. Loss of either domain inactivated PMR1 targeting to polysomes and stabilized albumin mRNA. The current study identified a phosphorylated tyrosine residue within the C-terminal polysome-targeting domain and showed that this modification is required for PMR1-mediated mRNA decay. Changing this tyrosine to phenylalanine inactivated the targeting of PMR1 to polysomes, blocked binding of PMR1 to the functional complex containing its substrate mRNA, prevented the targeting of a green fluorescent protein fusion protein to this complex, and stabilized albumin mRNA to degradation by PMR1 in vivo. A general tyrosine kinase inhibitor inhibited the phosphorylation of PMR1, which in turn inhibited PMR1-catalyzed degradation of albumin mRNA. These results indicate that one or more tyr...Continue Reading

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Citations

Mar 7, 2012·Nature Reviews. Genetics·Daniel R Schoenberg, Lynne E Maquat
Jan 25, 2007·Nature Reviews. Molecular Cell Biology·Nicole L GarneauCarol J Wilusz
Sep 20, 2006·Molecular and Cellular Biology·Feng YangDaniel R Schoenberg
Jun 21, 2013·PLoS Pathogens·Anne-Marie HansenAkhilesh Pandey
Apr 16, 2008·The Journal of Cell Biology·Christopher von Roretz, Imed-Eddine Gallouzi
Mar 29, 2012·Gene·Xiangyue Wu, Gary Brewer
Oct 1, 2011·Wiley Interdisciplinary Reviews. RNA·Daniel R Schoenberg
May 26, 2009·Biochimica Et Biophysica Acta·Wan-Cheol Kim, Chow H Lee
Mar 14, 2007·Molecular Cell·Yong Peng, Daniel R Schoenberg
Mar 13, 2014·Molecular & Cellular Proteomics : MCP·Cuauhtemoc Licona-CassaniLars K Nielsen

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