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Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters.

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.

SUBMITTER: Hung T

PROVIDER: S-EPMC3652667 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters.

Hung Tiffany T Wang Yulei Y Lin Michael F MF Koegel Ashley K AK Kotake Yojiro Y Grant Gavin D GD Horlings Hugo M HM Shah Nilay N Umbricht Christopher C Wang Pei P Wang Yu Y Kong Benjamin B Langerød Anita A Børresen-Dale Anne-Lise AL Kim Seung K SK van de Vijver Marc M Sukumar Saraswati S Whitfield Michael L ML Kellis Manolis M Xiong Yue Y Wong David J DJ Chang Howard Y HY

Nature genetics 20110605 7

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 ex ...[more]

PMID: 21642992

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Dataset Information

Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters.

Publications

Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters.

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