TY - JOUR
T1 - DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs
AU - Fukuda, Toru
AU - Yamagata, Kaoru
AU - Fujiyama, Sally
AU - Matsumoto, Takahiro
AU - Koshida, Iori
AU - Yoshimura, Kimihiro
AU - Mihara, Masatomo
AU - Naitou, Masanori
AU - Endoh, Hideki
AU - Nakamura, Takashi
AU - Akimoto, Chihiro
AU - Yamamoto, Yoko
AU - Katagiri, Takenobu
AU - Foulds, Charles
AU - Takezawa, Shinichiro
AU - Kitagawa, Hirochika
AU - Takeyama, Ken Ichi
AU - O'Malley, Bert W.
AU - Kato, Shigeaki
PY - 2007/5
Y1 - 2007/5
N2 - MicroRNAs (miRNAs) control cell proliferation, differentiation and fate through modulation of gene expression by partially base-pairing with target mRNA sequences. Drosha is an RNase III enzyme that is the catalytic subunit of a large complex that cleaves pri-miRNAs with distinct structures into pre-miRNAs. Here, we show that both the p68 and p72 DEAD-box RNA helicase subunits in the mouse Drosha complex are indispensable for survival in mice, and both are required for primary miRNA and rRNA processing. Gene disruption of either p68 or p72 in mice resulted in early lethality, and in both p68-/- and p72-/- embryos, expression levels of a set of, but not all, miRNAs and 5.8S rRNA were significantly lowered. In p72 MEF cells, expression of p72, but not a mutant lacking ATPase activity, restored the impaired expression of miRNAs and 5.8S rRNA. Furthermore, we purified the large complex of mouse Drosha and showed it could generate pre-miRNA and 5.8S rRNA in vitro. Thus, we suggest that DEAD-box RNA helicase subunits are required for recognition of a subset of primary miRNAs in mDrosha-mediated processing.
AB - MicroRNAs (miRNAs) control cell proliferation, differentiation and fate through modulation of gene expression by partially base-pairing with target mRNA sequences. Drosha is an RNase III enzyme that is the catalytic subunit of a large complex that cleaves pri-miRNAs with distinct structures into pre-miRNAs. Here, we show that both the p68 and p72 DEAD-box RNA helicase subunits in the mouse Drosha complex are indispensable for survival in mice, and both are required for primary miRNA and rRNA processing. Gene disruption of either p68 or p72 in mice resulted in early lethality, and in both p68-/- and p72-/- embryos, expression levels of a set of, but not all, miRNAs and 5.8S rRNA were significantly lowered. In p72 MEF cells, expression of p72, but not a mutant lacking ATPase activity, restored the impaired expression of miRNAs and 5.8S rRNA. Furthermore, we purified the large complex of mouse Drosha and showed it could generate pre-miRNA and 5.8S rRNA in vitro. Thus, we suggest that DEAD-box RNA helicase subunits are required for recognition of a subset of primary miRNAs in mDrosha-mediated processing.
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U2 - 10.1038/ncb1577
DO - 10.1038/ncb1577
M3 - Article
C2 - 17435748
AN - SCOPUS:34247876168
SN - 1465-7392
VL - 9
SP - 604
EP - 611
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 5
ER -