title: ADAR1 forms a complex with Dicer to promote microRNA processing and RNA-induced gene silencing.
abstract: Adenosine deaminases acting on RNA (ADARs) are involved in RNA editing that converts adenosine residues to inosine specifically in double-stranded RNAs. In this study, we investigated the interaction of the RNA editing mechanism with the RNA interference (RNAi) machinery and found that ADAR1 forms a complex with Dicer through direct protein-protein interaction. Most importantly, ADAR1 increases the maximum rate (Vmax) of pre-microRNA (miRNA) cleavage by Dicer and facilitates loading of miRNA onto RNA-induced silencing complexes, identifying a new role of ADAR1 in miRNA processing and RNAi mechanisms. ADAR1 differentiates its functions in RNA editing and RNAi by the formation of either ADAR1/ADAR1 homodimer or Dicer/ADAR1 heterodimer complexes, respectively. As expected, the expression of miRNAs is globally inhibited in ADAR1(-/-) mouse embryos, which, in turn, alters the expression of their target genes and might contribute to their embryonic lethal phenotype.
authors.affiliation: The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Ota
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sakurai
authors.forename: Ravi
authors.initials: R
authors.lastname: Gupta
authors.forename: Louis
authors.initials: L
authors.lastname: Valente
authors.forename: Bjorn-Erik
authors.initials: BE
authors.lastname: Wulff
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ariyoshi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Iizasa
authors.forename: Ramana V
authors.initials: RV
authors.lastname: Davuluri
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nishikura
mesh_terms: D000243:Adenosine Deaminase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D004622:Embryo, Mammalian / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D008969:Molecular Sequence Data; D054730:Protein Interaction Domains and Motifs; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins; D043244:Ribonuclease III / Q000737:chemistry / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; D053487:DEAD-box RNA Helicases