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ADAR1 forms a complex with Dicer to promote microRNA processing and RNA-induced gene silencing.

By H. Ota, M. Sakurai, R Gupta, L. Valente, B.E. Wulff, K. Ariyoshi, H. Iizasa, R.V. Davuluri and K. Nishikura

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

Year: 2013
DOI identifier: 10.1016/j.cell.2013.03.024
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Provided by: NARCIS
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