title: Competition between ADAR and RNAi pathways for an extensive class of RNA targets.
abstract: Adenosine deaminases that act on RNAs (ADARs) interact with double-stranded RNAs, deaminating adenosines to inosines. Previous studies of Caenorhabditis elegans indicated an antagonistic interaction between ADAR and RNAi machineries, with ADAR defects suppressed upon additional knockout of RNAi. This suggests a pool of common RNA substrates capable of engaging both pathways. To define and characterize such substrates, we examined small RNA and mRNA populations of ADAR mutants and identified a distinct set of loci from which RNAi-dependent short RNAs are markedly upregulated. At these same loci, we observed populations of multiply edited transcripts, supporting a specific role for ADARs in preventing access to the RNAi pathway for an extensive population of dsRNAs. Characterization of these loci revealed a substantial overlap with noncoding and intergenic regions, suggesting that the landscape of ADAR targets may extend beyond previously annotated classes of transcripts.
authors: Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
authors: Diane
authors: D
authors: Wu
authors: Ayelet T
authors: AT
authors: Lamm
authors: Andrew Z
authors: AZ
authors: Fire
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism*; D004251:DNA Transposable Elements; D015536:Down-Regulation; D012313:RNA / Q000378:metabolism*; D017393:RNA Editing; D034622:RNA Interference; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins
chemical_list: D004251:DNA Transposable Elements; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D012313:RNA; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase