Unbiased Identification of trans Regulators of ADAR and A-to-I RNA Editing.


Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
19 05 2020
Historique:
received: 31 01 2020
revised: 11 04 2020
accepted: 23 04 2020
entrez: 21 5 2020
pubmed: 21 5 2020
medline: 22 5 2021
Statut: ppublish

Résumé

Adenosine-to-inosine RNA editing is catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes that deaminate adenosine to inosine. Although many RNA editing sites are known, few trans regulators have been identified. We perform BioID followed by mass spectrometry to identify trans regulators of ADAR1 and ADAR2 in HeLa and M17 neuroblastoma cells. We identify known and novel ADAR-interacting proteins. Using ENCODE data, we validate and characterize a subset of the novel interactors as global or site-specific RNA editing regulators. Our set of novel trans regulators includes all four members of the DZF-domain-containing family of proteins: ILF3, ILF2, STRBP, and ZFR. We show that these proteins interact with each ADAR and modulate RNA editing levels. We find ILF3 is a broadly influential negative regulator of editing. This work demonstrates the broad roles that RNA binding proteins play in regulating editing levels, and establishes DZF-domain-containing proteins as a group of highly influential RNA editing regulators.

Identifiants

pubmed: 32433965
pii: S2211-1247(20)30609-4
doi: 10.1016/j.celrep.2020.107656
pmc: PMC7306178
mid: NIHMS1596751
pii:
doi:

Substances chimiques

RNA-Binding Proteins 0
ADAR protein, human EC 3.5.4.37
ADARB1 protein, human 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 Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

107656

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM124215
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH115080
Pays : United States
Organisme : NCRR NIH HHS
ID : P41 RR011823
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM102484
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007790
Pays : United States

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

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Auteurs

Emily C Freund (EC)

Department of Genetics, Stanford University, Stanford, CA 94305, USA.

Anne L Sapiro (AL)

Department of Genetics, Stanford University, Stanford, CA 94305, USA.

Qin Li (Q)

Department of Genetics, Stanford University, Stanford, CA 94305, USA.

Sandra Linder (S)

Department of Genetics, Stanford University, Stanford, CA 94305, USA.

James J Moresco (JJ)

Department of Molecular Medicine, 10550 North Torrey Pines Road, SR302, The Scripps Research Institute, La Jolla, CA 92037, USA.

John R Yates (JR)

Department of Molecular Medicine, 10550 North Torrey Pines Road, SR302, The Scripps Research Institute, La Jolla, CA 92037, USA.

Jin Billy Li (JB)

Department of Genetics, Stanford University, Stanford, CA 94305, USA. Electronic address: jin.billy.li@stanford.edu.

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Classifications MeSH