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 A. Hundley

Research output: Contribution to journalArticle

33 Scopus citations

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'The dsRBP and Inactive Editor ADR-1Utilizes dsRNA Binding to Regulate A-to-I RNA Editing across the C.elegans Transcriptome'. Together they form a unique fingerprint.

  • Cite this

    Washburn, M. C., Kakaradov, B., Sundararaman, B., Wheeler, E., Hoon, S., Yeo, G. W., & Hundley, H. A. (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