Modulation of microRNA processing and expression through RNA editing by ADAR deaminases.
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.
Yang
Weidong
W
The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
Chendrimada
Thimmaiah P
TP
Wang
Qingde
Q
Higuchi
Miyoko
M
Seeburg
Peter H
PH
Shiekhattar
Ramin
R
Nishikura
Kazuko
K
D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D017393:RNA Editing / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins; D043244:Ribonuclease III / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism
D035683:MicroRNAs; D016601:RNA-Binding Proteins; D043244:Ribonuclease III; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase