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PMID: 24508457 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

The dsRBP and inactive editor ADR-1 utilizes dsRNA binding to regulate A-to-I RNA editing across the C. elegans transcriptome.

Cell reports ·Vol. 6 ·No. 4 ·2014-02-27 ·Pages 599-607

Washburn MC, Kakaradov B, Sundararaman B, Wheeler E, Hoon S, Yeo GW, Hundley HA

Abstract

Inadequate adenosine-to-inosine editing of noncoding regions occurs in disease but is often uncorrelated with ADAR levels, underscoring the need to study deaminase-independent control of editing. C. elegans have two ADAR proteins, ADR-2 and the theoretically catalytically inactive ADR-1. Using high-throughput RNA sequencing of wild-type and adr mutant worms, we expand the repertoire of C. elegans edited transcripts over 5-fold and confirm that ADR-2 is the only active deaminase in vivo. Despite lacking deaminase function, ADR-1 affects editing of over 60 adenosines within the 3' UTRs of 16 different mRNAs. Furthermore, ADR-1 interacts directly with ADR-2 substrates, even in the absence of ADR-2, and mutations within its double-stranded RNA (dsRNA) binding domains abolish both binding and editing regulation. We conclude that ADR-1 acts as a major regulator of editing by binding ADR-2 substrates in vivo. These results raise the possibility that other dsRNA binding proteins, including the inactive human ADARs, regulate RNA editing through deaminase-independent mechanisms.

MeSH Terms
3' Untranslated Regions Adenosine/genetics,metabolism Adenosine Deaminase/genetics,metabolism Animals Binding Sites Caenorhabditis elegans/genetics,metabolism Caenorhabditis elegans Proteins/genetics,metabolism Inosine/genetics,metabolism Mutation Protein Binding RNA Editing RNA, Double-Stranded/chemistry,metabolism Transcriptome
Chemicals
3' Untranslated Regions Caenorhabditis elegans Proteins RNA, Double-Stranded Inosine Adenosine Deaminase Adr-1 protein, C elegans Adr-2 protein, C elegans Adenosine
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Washburn Michael C
Department of Biology, Indiana University, Bloomington, IN 47405, USA.
Kakaradov Boyko
Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093-0419, USA; Department of Cellular and Molecular Medicine, UCSD Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093-0651, USA.
Sundararaman Balaji
Department of Cellular and Molecular Medicine, UCSD Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093-0651, USA.
Wheeler Emily
Medical Sciences Program, Indiana University, Bloomington, IN 47405, USA.
Hoon Shawn
Molecular Engineering Laboratory, A(∗)STAR, Singapore 138673, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore 639798, Singapore.
Yeo Gene W
Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093-0419, USA; Department of Cellular and Molecular Medicine, UCSD Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093-0651, USA; Molecular Engineering Laboratory, A(∗)STAR, Singapore 138673, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore. Electronic address: [email protected].
Hundley Heather A
Medical Sciences Program, Indiana University, Bloomington, IN 47405, USA. Electronic address: [email protected].
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Article Info
Journal
Cell reports
Abbr.
Cell Rep
ISSN
2211-1247
DOI
10.1016/j.celrep.2014.01.011
Email
[email protected]
[email protected]
Published
2014-02-27
Epub
2014-00-06
Pages
599-607
Language
English
Region
United States
NLM ID
101573691
PMCID
PMC3959997
Subset
IM
Grants
NIGMS NIH HHS · T32 GM007757 · United States
NHGRI NIH HHS · R01 HG004659 · United States
NCI NIH HHS · P30 CA023100 · United States
NIGMS NIH HHS · T32 GM008666 · United States
NINDS NIH HHS · R01 NS075449 · United States
Databases
GEO
GSE51556
External Links
PubMed source DOI: 10.1016/j.celrep.2014.01.011 PMC Full Text View journal details
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