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

@article{citeulike:1246616, 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.}, address = {[1] Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-0032, Japan. [2] These authors contributed equally to this work.}, author = {Fukuda, Toru and Yamagata, Kaoru and Fujiyama, Sally and Matsumoto, Takahiro and Koshida, Iori and Yoshimura, Kimihiro and Mihara, Masatomo and Naitou, Masanori and Endoh, Hideki and Nakamura, Takashi and Akimoto, Chihiro and Yamamoto, Yoko and Katagiri, Takenobu and Foulds, Charles and Takezawa, Shinichiro and Kitagawa, Hirochika and Takeyama, Ken-Ichi I. and O'malley, Bert W W. and Kato, Shigeaki }, citeulike-article-id = {1246616}, doi = {http://dx.doi.org/10.1038/ncb1577}, issn = {1465-7392}, journal = {Nat Cell Biol}, keywords = {microrna}, month = {April}, posted-at = {2007-04-24 05:02:38}, priority = {2}, title = {DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs.}, url = {http://dx.doi.org/10.1038/ncb1577}, year = {2007} }

TY - JOUR ID - citeulike:1246616 L3 - citeulike-article-id:1246616 TI - DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs. JF - Nat Cell Biol AD - [1] Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-0032, Japan. [2] These authors contributed equally to this work. SN - 1465-7392 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. KW - microrna 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 - 2007/04/15/ UR - http://dx.doi.org/10.1038/ncb1577 ER -