The dsRBP and Inactive Editor ADR-1 Utilizes dsRNA Binding to Regulate A-to-I RNA Editing across the C. elegans Transcriptome

The dsRBP and Inactive Editor ADR-1 Utilizes dsRNA Binding to Regulate A-to-I RNA Editing across the C. elegans Transcriptome

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-...

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Main Authors: Michael C. Washburn, Boyko Kakaradov, Balaji Sundararaman, Emily Wheeler, Shawn Hoon, Gene W. Yeo, Heather A. Hundley
Format: Article
Language:English
Published: Elsevier 2014-02-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S221112471400028X
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spelling doaj-41e2f6164f6b4788a9c7ae674b1770672020-11-24T21:47:27ZengElsevierCell Reports2211-12472014-02-016459960710.1016/j.celrep.2014.01.011The dsRBP and Inactive Editor ADR-1 Utilizes dsRNA Binding to Regulate A-to-I RNA Editing across the C. elegans TranscriptomeMichael C. Washburn0Boyko Kakaradov1Balaji Sundararaman2Emily Wheeler3Shawn Hoon4Gene W. Yeo5Heather A. Hundley6Department of Biology, Indiana University, Bloomington, IN 47405, USABioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093-0419, USADepartment of Cellular and Molecular Medicine, UCSD Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093-0651, USAMedical Sciences Program, Indiana University, Bloomington, IN 47405, USAMolecular Engineering Laboratory, A∗STAR, Singapore 138673, SingaporeBioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093-0419, USAMedical Sciences Program, Indiana University, Bloomington, IN 47405, USAInadequate 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.http://www.sciencedirect.com/science/article/pii/S221112471400028X
collection DOAJ
language English
format Article
sources DOAJ
author Michael C. Washburn
Boyko Kakaradov
Balaji Sundararaman
Emily Wheeler
Shawn Hoon
Gene W. Yeo
Heather A. Hundley
spellingShingle Michael C. Washburn
Boyko Kakaradov
Balaji Sundararaman
Emily Wheeler
Shawn Hoon
Gene W. Yeo
Heather A. Hundley
The dsRBP and Inactive Editor ADR-1 Utilizes dsRNA Binding to Regulate A-to-I RNA Editing across the C. elegans Transcriptome
Cell Reports
author_facet Michael C. Washburn
Boyko Kakaradov
Balaji Sundararaman
Emily Wheeler
Shawn Hoon
Gene W. Yeo
Heather A. Hundley
author_sort Michael C. Washburn
title The dsRBP and Inactive Editor ADR-1 Utilizes dsRNA Binding to Regulate A-to-I RNA Editing across the C. elegans Transcriptome
title_short The dsRBP and Inactive Editor ADR-1 Utilizes dsRNA Binding to Regulate A-to-I RNA Editing across the C. elegans Transcriptome
title_full The dsRBP and Inactive Editor ADR-1 Utilizes dsRNA Binding to Regulate A-to-I RNA Editing across the C. elegans Transcriptome
title_fullStr The dsRBP and Inactive Editor ADR-1 Utilizes dsRNA Binding to Regulate A-to-I RNA Editing across the C. elegans Transcriptome
title_full_unstemmed The dsRBP and Inactive Editor ADR-1 Utilizes dsRNA Binding to Regulate A-to-I RNA Editing across the C. elegans Transcriptome
title_sort dsrbp and inactive editor adr-1 utilizes dsrna binding to regulate a-to-i rna editing across the c. elegans transcriptome
publisher Elsevier
series Cell Reports
issn 2211-1247
publishDate 2014-02-01
description 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.
url http://www.sciencedirect.com/science/article/pii/S221112471400028X
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