Antagonistic and stimulative roles of ADAR1 in RNA silencing: An editor's point-of-view

Kazuko Nishikura, Masayuki Sakurai, Kantaro Ariyoshi, Hiromitsu Ota

Research output: Contribution to journalReview articlepeer-review

14 Citations (Scopus)

Abstract

Adenosine deaminases acting on RNA (ADARs) are involved in RNA editing that converts adenosine residues to inosine specifically in double-stranded RNAs (dsRNA). This A-to-I RNA editing pathway and the RNA interference (RNAi) pathway seem to interact antagonistically by competing for their common dsRNA substrates. For instance, A-to-I editing of certain microRNA (miRNA) precursors by ADAR1 and ADAR2 inhibits their processing to mature miRNAs. Recent studies unexpectedly revealed the presence of a completely different type of interaction between the RNA editing mechanism and the RNAi machinery. ADAR1 forms a complex via direct protein-protein interaction with Dicer, an RNase III gene family member involved in the RNAi mechanism. ADAR1 in the Dicer complex promotes pre-miRNA cleavage by Dicer and facilitates loading of miRNA onto RNAinduced silencing complexes, giving rise to an unsuspected stimulative function of ADAR1 on miRNA processing and RNAi mechanisms. ADAR1 differentiates its functions in RNA editing and RNAi by formation of either ADAR1-ADAR1 homodimer or Dicer-ADAR1 heterodimer complexes. Expression of miRNAs is globally inhibited in ADAR1-null mouse embryos, which, in turn, alters expression of their target genes and may contribute to their embryonic lethal phenotype.

Original languageEnglish
Pages (from-to)1240-1247
Number of pages8
JournalRNA Biology
Volume10
Issue number8
DOIs
Publication statusPublished - 2013 Jan 1

Keywords

  • ADAR1
  • Apoptosis
  • Dicer
  • DsRNA
  • Embryo development
  • MiRNA biogenesis
  • MiRNA targets
  • RISC
  • RNA editing
  • RNAi

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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