MicroRNAs (miRNAs) control cell proliferation, differentiation and fate through modulation of gene expression by partially base-pairing with target mRNA sequences^{1, 2, 3, 4, 5, 6}. Drosha is an RNase III enzyme that is the catalytic subunit of a large complex that cleaves pri-miRNAs with distinct structures into pre-miRNAs⁷. Here, we show that both the p68 and p72 DEAD-box RNA helicase subunits^{8, 9, 10} 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.

1. Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-0032, Japan.
2. ERATO, Japan Science and Technology, Honcho 4-1-8, Kawaguchi, Saitama 332-0012, Japan.
3. Applied Genomics, Molecular Medicine Labs., Drug Discovery Research, Astellas Pharma Inc., 21,Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan.
4. Research Center for Genomic Medicine, Saitama Medical School, Yamane 1397-1, Hidakashi, Saitama, 350-1242, Japan.
5. Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
6. These authors contributed equally to this work.

Correspondence to: Shigeaki Kato^1,2 e-mail: uskato@mail.ecc.u-tokyo.ac.jp

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