Washington University in St. Louis

New Publication in JBC for You Lab

Congratulations to Andrew Nickless in Zhongsheng You's lab on his first-author paper.  The You lab in collaboration with colleague, Sheila Stewart published their work in the Journal of Biological Chemistry.

Andrew Nickless, Abigael Cheruiyot, Kevin C. Flanagan, David Piwnica-Worms, Sheila A. Stewart, and Zhongsheng You  (2017)  p38 MAPK Inhibits Nonsense-mediated RNA Decay in Response to Persistent DNA Damange In Non-cycling Cells.  J. Biol. Chem. doi:10.1074//jbc.M117.787846.  [E-published August 1]

Abstract:  Persistent DNA damage induces profound alterations in gene expression, which in turn influence tissue homeostasis, tumorigenesis, and cancer treatment outcome. However, the underlying mechanism for the gene expression reprogramming induced by persistent DNA damage remains poorly understood. Here, using a highly effective bioluminescence-based reporter system and other tools, we report that persistent DNA damage inhibits nonsense-mediated RNA decay (NMD), an RNA surveillance and gene-regulatory pathway, in noncycling cells. NMD suppression by persistent DNA damage required the activity of the p38α MAPK. Activating transcription factor 3 (ATF3), an NMD target and a key stress-inducible transcription factor, was stabilized in a p38α- and NMD-dependent manner following persistent DNA damage. Our results reveal a novel p38α-dependent pathway that regulates NMD activity in response to persistent DNA damage, which in turn controls ATF3 expression in affected cells.

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