ADAR1 RNA editing enzyme regulates R-loop formation and genome stability at telomeres in cancer cells.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 03 2021
12 03 2021
Historique:
received:
28
05
2020
accepted:
19
02
2021
entrez:
13
3
2021
pubmed:
14
3
2021
medline:
2
4
2021
Statut:
epublish
Résumé
ADAR1 is involved in adenosine-to-inosine RNA editing. The cytoplasmic ADAR1p150 edits 3'UTR double-stranded RNAs and thereby suppresses induction of interferons. Loss of this ADAR1p150 function underlies the embryonic lethality of Adar1 null mice, pathogenesis of the severe autoimmune disease Aicardi-Goutières syndrome, and the resistance developed in cancers to immune checkpoint blockade. In contrast, the biological functions of the nuclear-localized ADAR1p110 remain largely unknown. Here, we report that ADAR1p110 regulates R-loop formation and genome stability at telomeres in cancer cells carrying non-canonical variants of telomeric repeats. ADAR1p110 edits the A-C mismatches within RNA:DNA hybrids formed between canonical and non-canonical variant repeats. Editing of A-C mismatches to I:C matched pairs facilitates resolution of telomeric R-loops by RNase H2. This ADAR1p110-dependent control of telomeric R-loops is required for continued proliferation of telomerase-reactivated cancer cells, revealing the pro-oncogenic nature of ADAR1p110 and identifying ADAR1 as a promising therapeutic target of telomerase positive cancers.
Identifiants
pubmed: 33712600
doi: 10.1038/s41467-021-21921-x
pii: 10.1038/s41467-021-21921-x
pmc: PMC7955049
doi:
Substances chimiques
RNA-Binding Proteins
0
DNA
9007-49-2
ADAR protein, human
EC 3.5.4.37
ADAR1 protein, mouse
EC 3.5.4.4
Adenosine Deaminase
EC 3.5.4.4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1654Subventions
Organisme : NCI NIH HHS
ID : P30 CA010815
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA175058
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM040536
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM130716
Pays : United States
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