Cell Reports (Feb 2014)

The dsRBP and Inactive Editor ADR-1 Utilizes 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

DOI
https://doi.org/10.1016/j.celrep.2014.01.011
Journal volume & issue
Vol. 6, no. 4
pp. 599 – 607

Abstract

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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.