ミシマ ユウイチロウ   Mishima Yuichiro
  三嶋 雄一郎
   所属   京都産業大学  生命科学部 先端生命科学科
   職種   教授
言語種別 英語
発行・発表の年月 2010/06
形態種別 研究論文
査読 査読あり
標題 A Novel miRNA Processing Pathway Independent of Dicer Requires Argonaute2 Catalytic Activity
執筆形態 その他
掲載誌名 SCIENCE
出版社・発行元 AMER ASSOC ADVANCEMENT SCIENCE
巻・号・頁 328(5986),pp.1694-1698
著者・共著者 Daniel Cifuentes,Huiling Xue,David W. Taylor,Heather Patnode,Yuichiro Mishima,Sihem Cheloufi,Enbo Ma,Shrikant Mane,Gregory J. Hannon,Nathan D. Lawson,Scot A. Wolfe,Antonio J. Giraldez
概要 Dicer is a central enzyme in microRNA (miRNA) processing. We identified a Dicer-independent miRNA biogenesis pathway that uses Argonaute2 (Ago2) slicer catalytic activity. In contrast to other miRNAs, miR-451 levels were refractory to dicer loss of function but were reduced in MZago2 (maternal-zygotic) mutants. We found that pre-miR-451 processing requires Ago2 catalytic activity in vivo. MZago2 mutants showed delayed erythropoiesis that could be rescued by wild-type Ago2 or miR-451-duplex but not by catalytically dead Ago2. Changing the secondary structure of Dicer-dependent miRNAs to mimic that of pre-miR-451 restored miRNA function and rescued developmental defects in MZdicer mutants, indicating that the pre-miRNA secondary structure determines the processing pathway in vivo. We propose that Ago2-mediated cleavage of pre-miRNAs, followed by uridylation and trimming, generates functional miRNAs independently of Dicer.
DOI 10.1126/science.1190809
ISSN 0036-8075
PMID 20448148