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

ABSTRACT: 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.

SUBMITTER: Zhang X

PROVIDER: S-EPMC3114434 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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

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

Molecular cell 20110201 4

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 ...[more]

PMID: 21329876

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2016-10-12 | PXD003712 | Pride

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