期刊
MOLECULAR CELL
卷 41, 期 4, 页码 371-383出版社
CELL PRESS
DOI: 10.1016/j.molcel.2011.01.020
关键词
-
资金
- National Institutes of Health [R01CA136549, R03CA142605, P20RR017698]
- American Cancer Society [119135-RSG-10-185-01-TBE]
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.
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