Nature Structural & Molecular Biology 13, 13 - 21 (2005)
Published online: 20 December 2005; | doi:10.1038/nsmb1041
Modulation of microRNA processing and expression through RNA editing by ADAR deaminasesWeidong Yang1, Thimmaiah P Chendrimada1, Qingde Wang1, Miyoko Higuchi2, Peter H Seeburg2, Ramin Shiekhattar1
& Kazuko Nishikura11
The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA. 2
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, D-69120, Heidelberg, Germany.
Correspondence should be addressed to Kazuko Nishikura kazuko@wistar.org Adenosine deaminases acting on RNA (ADARs) are involved in editing of adenosine residues to inosine in double-stranded RNA (dsRNA). Although this editing recodes and alters functions of several mammalian genes, its most common targets are noncoding repeat sequences, indicating the involvement of this editing system in currently unknown functions other than recoding of protein sequences. Here we show that specific adenosine residues of certain microRNA (miRNA) precursors are edited by ADAR1 and ADAR2. Editing of pri–miR-142, the precursor of miRNA-142, expressed in hematopoietic tissues, resulted in suppression of its processing by Drosha. The edited pri–miR-142 was degraded by Tudor-SN, a component of RISC and also a ribonuclease specific to inosine-containing dsRNAs. Consequently, mature miRNA-142 expression levels increased substantially in ADAR1 null or ADAR2 null mice. Our results demonstrate a new function of RNA editing in the control of miRNA biogenesis.
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