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

Michael C. Washburn, Boyko Kakaradov, Balaji Sundararaman, Emily Wheeler, Shawn Hoon, Gene W. Yeo, Heather Hundley

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Inadequate adenosine-to-inosine editing of noncoding regions occurs in disease but is often uncorrelated with ADAR levels, underscoring the need tostudy deaminase-independent control of editing. C.elegans have two ADAR proteins, ADR-2 and thetheoretically 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 invivo. 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 invivo. These results raise the possibility that other dsRNA binding proteins, including the inactive human ADARs, regulate RNA editing through deaminase-independent mechanisms.

Original languageEnglish
Pages (from-to)599-607
Number of pages9
JournalCell Reports
Volume6
Issue number4
DOIs
StatePublished - 2014

Fingerprint

RNA Editing
Double-Stranded RNA
Transcriptome
Adenosine
RNA
High-Throughput Nucleotide Sequencing
Inosine
RNA-Binding Proteins
3' Untranslated Regions
Substrates
Throughput
Messenger RNA
Mutation
Proteins
immune RNA
Double-Stranded RNA Binding Motif

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Washburn, M. C., Kakaradov, B., Sundararaman, B., Wheeler, E., Hoon, S., Yeo, G. W., & Hundley, H. (2014). The dsRBP and Inactive Editor ADR-1Utilizes dsRNA Binding to Regulate A-to-I RNA Editing across the C.elegans Transcriptome. Cell Reports, 6(4), 599-607. https://doi.org/10.1016/j.celrep.2014.01.011

The dsRBP and Inactive Editor ADR-1Utilizes dsRNA Binding to Regulate A-to-I RNA Editing across the C.elegans Transcriptome. / Washburn, Michael C.; Kakaradov, Boyko; Sundararaman, Balaji; Wheeler, Emily; Hoon, Shawn; Yeo, Gene W.; Hundley, Heather.

In: Cell Reports, Vol. 6, No. 4, 2014, p. 599-607.

Research output: Contribution to journalArticle

Washburn, MC, Kakaradov, B, Sundararaman, B, Wheeler, E, Hoon, S, Yeo, GW & Hundley, H 2014, 'The dsRBP and Inactive Editor ADR-1Utilizes dsRNA Binding to Regulate A-to-I RNA Editing across the C.elegans Transcriptome', Cell Reports, vol. 6, no. 4, pp. 599-607. https://doi.org/10.1016/j.celrep.2014.01.011
Washburn, Michael C. ; Kakaradov, Boyko ; Sundararaman, Balaji ; Wheeler, Emily ; Hoon, Shawn ; Yeo, Gene W. ; Hundley, Heather. / The dsRBP and Inactive Editor ADR-1Utilizes dsRNA Binding to Regulate A-to-I RNA Editing across the C.elegans Transcriptome. In: Cell Reports. 2014 ; Vol. 6, No. 4. pp. 599-607.
@article{691018416905441c91d145843b17f18e,
title = "The dsRBP and Inactive Editor ADR-1Utilizes dsRNA Binding to Regulate A-to-I RNA Editing across the C.elegans Transcriptome",
abstract = "Inadequate adenosine-to-inosine editing of noncoding regions occurs in disease but is often uncorrelated with ADAR levels, underscoring the need tostudy deaminase-independent control of editing. C.elegans have two ADAR proteins, ADR-2 and thetheoretically 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 invivo. 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 invivo. These results raise the possibility that other dsRNA binding proteins, including the inactive human ADARs, regulate RNA editing through deaminase-independent mechanisms.",
author = "Washburn, {Michael C.} and Boyko Kakaradov and Balaji Sundararaman and Emily Wheeler and Shawn Hoon and Yeo, {Gene W.} and Heather Hundley",
year = "2014",
doi = "10.1016/j.celrep.2014.01.011",
language = "English",
volume = "6",
pages = "599--607",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",

}

TY - JOUR

T1 - The dsRBP and Inactive Editor ADR-1Utilizes dsRNA Binding to Regulate A-to-I RNA Editing across the C.elegans Transcriptome

AU - Washburn, Michael C.

AU - Kakaradov, Boyko

AU - Sundararaman, Balaji

AU - Wheeler, Emily

AU - Hoon, Shawn

AU - Yeo, Gene W.

AU - Hundley, Heather

PY - 2014

Y1 - 2014

N2 - Inadequate adenosine-to-inosine editing of noncoding regions occurs in disease but is often uncorrelated with ADAR levels, underscoring the need tostudy deaminase-independent control of editing. C.elegans have two ADAR proteins, ADR-2 and thetheoretically 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 invivo. 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 invivo. These results raise the possibility that other dsRNA binding proteins, including the inactive human ADARs, regulate RNA editing through deaminase-independent mechanisms.

AB - Inadequate adenosine-to-inosine editing of noncoding regions occurs in disease but is often uncorrelated with ADAR levels, underscoring the need tostudy deaminase-independent control of editing. C.elegans have two ADAR proteins, ADR-2 and thetheoretically 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 invivo. 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 invivo. These results raise the possibility that other dsRNA binding proteins, including the inactive human ADARs, regulate RNA editing through deaminase-independent mechanisms.

UR - http://www.scopus.com/inward/record.url?scp=84896730394&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84896730394&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2014.01.011

DO - 10.1016/j.celrep.2014.01.011

M3 - Article

VL - 6

SP - 599

EP - 607

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 4

ER -