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An inducible long noncoding RNA amplifies DNA damage signaling.

ABSTRACT: Long noncoding RNAs (lncRNAs) are prevalent genes with frequently precise regulation but mostly unknown functions. Here we demonstrate that lncRNAs guide the organismal DNA damage response. DNA damage activated transcription of the DINO (Damage Induced Noncoding) lncRNA via p53. DINO was required for p53-dependent gene expression, cell cycle arrest and apoptosis in response to DNA damage, and DINO expression was sufficient to activate damage signaling and cell cycle arrest in the absence of DNA damage. DINO bound to p53 protein and promoted its stabilization, mediating a p53 auto-amplification loop. Dino knockout or promoter inactivation in mice dampened p53 signaling and ameliorated acute radiation syndrome in vivo. Thus, inducible lncRNA can create a feedback loop with its cognate transcription factor to amplify cellular signaling networks.

SUBMITTER: Schmitt AM

PROVIDER: S-EPMC5083181 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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An inducible long noncoding RNA amplifies DNA damage signaling.

Schmitt Adam M AM Garcia Julia T JT Hung Tiffany T Flynn Ryan A RA Shen Ying Y Qu Kun K Payumo Alexander Y AY Peres-da-Silva Ashwin A Broz Daniela Kenzelmann DK Baum Rachel R Guo Shuling S Chen James K JK Attardi Laura D LD Chang Howard Y HY

Nature genetics 20160926 11

Long noncoding RNAs (lncRNAs) are prevalent genes with frequently precise regulation but mostly unknown functions. Here we demonstrate that lncRNAs guide the organismal DNA damage response. DNA damage activated transcription of the DINO (Damage Induced Noncoding) lncRNA via p53. DINO was required for p53-dependent gene expression, cell cycle arrest and apoptosis in response to DNA damage, and DINO expression was sufficient to activate damage signaling and cell cycle arrest in the absence of DNA ...[more]

PMID: 27668660

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