期刊
EMBO JOURNAL
卷 31, 期 23, 页码 4415-4427出版社
WILEY
DOI: 10.1038/emboj.2012.292
关键词
cell-cycle progression; Cdk6; gadd7; IncRNA; TDP-43
资金
- 973 National Fundamental Research Program of China [2009CB521801, 2010CB912800]
- National Natural Science Foundation of China [81021061]
Long non-coding RNAs (IncRNAs) transcribed extensively from the genome have been proposed to be key regulators of diverse biological processes. However, little is known about the role of IncRNAs in regulation of the cell-cycle G1/S checkpoint following DNA damage, a key step in the maintenance of genomic fidelity. Here we show that growth-arrested DNA damage-inducible gene 7 (gadd7), a DNA damage-inducible IncRNA, regulates the G1/S checkpoint in response to UV irradiation. Interestingly, UV-induced gadd7 directly binds to TAR DNA-binding protein (TDP-43) and interferes with the interaction between TDP-43 and cyclin-dependent kinase 6 (Cdk6) mRNA, resulting in Cdk6 mRNA degradation. These findings demonstrate a role for gadd7 in controlling cell-cycle progression and define a novel mechanism by which IncRNAs modulate mRNA expression at the post-transcriptional level by altering mRNA stability. The EMBO Journal (2012) 31, 4415-4427. doi:10.1038/emboj.2012.292; Published online 26 October 2012
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