Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters
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Kellis_Extensive and.pdf
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Author(s)
Hung, Tiffany
Wang, Yulei
Lin, Michael F.
Koegel, Ashley K.
Kotake, Yojiro
Grant, Gavin D.
Horlings, Hugo M.
Shah, Nilay
Umbricht, Christopher
Wang, Pei
Date Issued
June 2011
Journal
Nature Genetics
Publisher
Nature Publishing Group
Citation
Hung, Tiffany, Yulei Wang, Michael F Lin, Ashley K Koegel, Yojiro Kotake, Gavin D Grant, Hugo M Horlings, et al. “Extensive and Coordinated Transcription of Noncoding RNAs Within Cell-Cycle Promoters.” Nature Genetics 43, no. 7 (June 5, 2011): 621–629.
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Author's final manuscript
Abstract
Transcription of long noncoding RNAs (lncRNAs) within gene regulatory elements can modulate gene activity in response to external stimuli, but the scope and functions of such activity are not known. Here we use an ultrahigh-density array that tiles the promoters of 56 cell-cycle genes to interrogate 108 samples representing diverse perturbations. We identify 216 transcribed regions that encode putative lncRNAs, many with RT-PCR–validated periodic expression during the cell cycle, show altered expression in human cancers and are regulated in expression by specific oncogenic stimuli, stem cell differentiation or DNA damage. DNA damage induces five lncRNAs from the CDKN1A promoter, and one such lncRNA, named PANDA, is induced in a p53-dependent manner. PANDA interacts with the transcription factor NF-YA to limit expression of pro-apoptotic genes; PANDA depletion markedly sensitized human fibroblasts to apoptosis by doxorubicin. These findings suggest potentially widespread roles for promoter lncRNAs in cell-growth control.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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DOI of Published Version
https://doi.org/10.1038/ng.848
