ADAR1 forms a complex with Dicer to promote microRNA processing and RNA-induced gene silencing.
Cell, 2013/4/25;153(3):575-89.
Ota H[1], Sakurai M, Gupta R, Valente L, Wulff BE, Ariyoshi K, Iizasa H, Davuluri RV, Nishikura K
Affiliations
PMID: 23622242
Impact factor: 66.85
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.
MeSH terms
Adenosine Deaminase; Animals; Base Sequence; DEAD-box RNA Helicases; Dimerization; Embryo, Mammalian; HEK293 Cells; HeLa Cells; Humans; Mice; MicroRNAs; Molecular Sequence Data; Protein Interaction Domains and Motifs; RNA Interference; RNA Processing, Post-Transcriptional; RNA, Small Interfering; RNA-Binding Proteins; Ribonuclease III; Up-Regulation
More resources
Full text:
Europe PubMed Central; PubMed Central
EndNote: Download