DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs

Toru Fukuda, Kaoru Yamagata, Sally Fujiyama, Takahiro Matsumoto, Iori Koshida, Kimihiro Yoshimura, Masatomo Mihara, Masanori Naitou, Hideki Endoh, Takashi Nakamura, Chihiro Akimoto, Yoko Yamamoto, Takenobu Katagiri, Charles Foulds, Shinichiro Takezawa, Hirochika Kitagawa, Ken Ichi Takeyama, Bert W. O'Malley, Shigeaki Kato

Research output: Contribution to journalArticle

314 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)604-611
Number of pages8
JournalNature Cell Biology
Volume9
Issue number5
DOIs
Publication statusPublished - 2007 May
Externally publishedYes

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DEAD-box RNA Helicases
MicroRNAs
Ribonuclease III
Base Pairing
Adenosine Triphosphatases
Cell Differentiation
Catalytic Domain
Embryonic Structures
Cell Proliferation
Gene Expression

ASJC Scopus subject areas

  • Cell Biology

Cite this

Fukuda, T., Yamagata, K., Fujiyama, S., Matsumoto, T., Koshida, I., Yoshimura, K., ... Kato, S. (2007). DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs. Nature Cell Biology, 9(5), 604-611. https://doi.org/10.1038/ncb1577

DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs. / Fukuda, Toru; Yamagata, Kaoru; Fujiyama, Sally; Matsumoto, Takahiro; Koshida, Iori; Yoshimura, Kimihiro; Mihara, Masatomo; Naitou, Masanori; Endoh, Hideki; Nakamura, Takashi; Akimoto, Chihiro; Yamamoto, Yoko; Katagiri, Takenobu; Foulds, Charles; Takezawa, Shinichiro; Kitagawa, Hirochika; Takeyama, Ken Ichi; O'Malley, Bert W.; Kato, Shigeaki.

In: Nature Cell Biology, Vol. 9, No. 5, 05.2007, p. 604-611.

Research output: Contribution to journalArticle

Fukuda, T, Yamagata, K, Fujiyama, S, Matsumoto, T, Koshida, I, Yoshimura, K, Mihara, M, Naitou, M, Endoh, H, Nakamura, T, Akimoto, C, Yamamoto, Y, Katagiri, T, Foulds, C, Takezawa, S, Kitagawa, H, Takeyama, KI, O'Malley, BW & Kato, S 2007, 'DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs', Nature Cell Biology, vol. 9, no. 5, pp. 604-611. https://doi.org/10.1038/ncb1577
Fukuda, Toru ; Yamagata, Kaoru ; Fujiyama, Sally ; Matsumoto, Takahiro ; Koshida, Iori ; Yoshimura, Kimihiro ; Mihara, Masatomo ; Naitou, Masanori ; Endoh, Hideki ; Nakamura, Takashi ; Akimoto, Chihiro ; Yamamoto, Yoko ; Katagiri, Takenobu ; Foulds, Charles ; Takezawa, Shinichiro ; Kitagawa, Hirochika ; Takeyama, Ken Ichi ; O'Malley, Bert W. ; Kato, Shigeaki. / DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs. In: Nature Cell Biology. 2007 ; Vol. 9, No. 5. pp. 604-611.
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