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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.

journal_name

Nat Genet

journal_title

Nature genetics

authors

Schmitt AM,Garcia JT,Hung T,Flynn RA,Shen Y,Qu K,Payumo AY,Peres-da-Silva A,Broz DK,Baum R,Guo S,Chen JK,Attardi LD,Chang HY

doi

10.1038/ng.3673

subject

Has Abstract

pub_date

2016-11-01 00:00:00

pages

1370-1376

issue

11

eissn

1061-4036

issn

1546-1718

pii

ng.3673

journal_volume

48

pub_type

杂志文章

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