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The ATM kinase induces microRNA biogenesis in the DNA damage response.

Xinna X Zhang, Guohui G Wan, Franklin G FG Berger, Xiaoming X He, and Xiongbin X Lu

Mol Cell 41(4):371-83 (2011) PMID 21329876

The DNA damage response involves a complex network of processes that detect and repair DNA damage. Here we show that miRNA biogenesis is globally induced upon DNA damage in an ATM-dependent manner. About one-fourth of miRNAs are significantly upregulated after DNA damage, while loss of ATM abolishes their induction. KH-type splicing regulatory protein (KSRP) is a key player that translates DNA damage signaling to miRNA biogenesis. The ATM kinase directly binds to and phosphorylates KSRP, leading to enhanced interaction between KSRP and pri-miRNAs and increased KSRP activity in miRNA processing. Mutations of the ATM phosphorylation sites of KSRP impaired its activity in regulating miRNAs. These findings reveal a mechanism by which DNA damage signaling is linked to miRNA biogenesis.

Copyright © 2011 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.molcel.2011.01.020
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