An inducible long noncoding RNA amplifies DNA damage signaling
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:48 |
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| Enthalten in: |
Nature genetics - 48(2016), 11 vom: 20. Nov., Seite 1370-1376 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schmitt, Adam M [VerfasserIn] |
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| Links: |
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| Themen: |
DINOL lncRNA, human |
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| Anmerkungen: |
Date Completed 08.09.2017 Date Revised 16.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/ng.3673 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM264699890 |
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| 245 | 1 | 3 | |a An inducible long noncoding RNA amplifies DNA damage signaling |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a DINOL lncRNA, human |2 NLM | |
| 650 | 7 | |a RNA, Long Noncoding |2 NLM | |
| 650 | 7 | |a TP53 protein, human |2 NLM | |
| 650 | 7 | |a Tumor Suppressor Protein p53 |2 NLM | |
| 700 | 1 | |a Garcia, Julia T |e verfasserin |4 aut | |
| 700 | 1 | |a Hung, Tiffany |e verfasserin |4 aut | |
| 700 | 1 | |a Flynn, Ryan A |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Qu, Kun |e verfasserin |4 aut | |
| 700 | 1 | |a Payumo, Alexander Y |e verfasserin |4 aut | |
| 700 | 1 | |a Peres-da-Silva, Ashwin |e verfasserin |4 aut | |
| 700 | 1 | |a Broz, Daniela Kenzelmann |e verfasserin |4 aut | |
| 700 | 1 | |a Baum, Rachel |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Shuling |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, James K |e verfasserin |4 aut | |
| 700 | 1 | |a Attardi, Laura D |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Howard Y |e verfasserin |4 aut | |
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