Modulation of microRNA processing and expression through RNA editing by ADAR deaminases

Weidong Yang, Thimmaiah P. Chendrimada, Qingde Wang, Miyoko Higuchi, Peter H. Seeburg, Ramin Shiekhattar, Kazuko Nishikura

Research output: Contribution to journalArticle

505 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)13-21
Number of pages9
JournalNature Structural and Molecular Biology
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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