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Link to original content: https://doi.org/10.1038/nature01957
The nuclear RNase III Drosha initiates microRNA processing | Nature
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The nuclear RNase III Drosha initiates microRNA processing

Nature volume 425, pages 415–419 (2003)Cite this article

Abstract

Hundreds of small RNAs of ∼22 nucleotides, collectively named microRNAs (miRNAs), have been discovered recently in animals and plants1,2,3,4,5,6,7,8,9,10. Although their functions are being unravelled1,2,11,12,13, their mechanism of biogenesis remains poorly understood. miRNAs are transcribed as long primary transcripts (pri-miRNAs) whose maturation occurs through sequential processing events: the nuclear processing of the pri-miRNAs into stem-loop precursors of ∼70 nucleotides (pre-miRNAs), and the cytoplasmic processing of pre-miRNAs into mature miRNAs14. Dicer, a member of the RNase III superfamily of bidentate nucleases, mediates the latter step15,16,17,18,19, whereas the processing enzyme for the former step is unknown. Here we identify another RNase III, human Drosha, as the core nuclease that executes the initiation step of miRNA processing in the nucleus. Immunopurified Drosha cleaved pri-miRNA to release pre-miRNA in vitro. Furthermore, RNA interference of Drosha resulted in the strong accumulation of pri-miRNA and the reduction of pre-miRNA and mature miRNA in vivo. Thus, the two RNase III proteins, Drosha and Dicer, may collaborate in the stepwise processing of miRNAs, and have key roles in miRNA-mediated gene regulation in processes such as development and differentiation.

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Figure 1: Cleavage sites and cis-acting requirements for the initiation step of miRNA processing.
Figure 2: In vitro processing of miRNA by Drosha.
Figure 3: In vitro processing activities of Drosha and Dicer.
Figure 4: In vivo function of Drosha.

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Acknowledgements

We are grateful to members of our laboratory and to K. Mitrophanous, J. M. Park and H. E. Kim for their critical reading of this manuscript and for discussion. This work was supported by the Korea Research Foundation and the BK21 Research Fellowship from the Ministry of Education and Human Resources Development of Korea.

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Authors and Affiliations

  1. Institute of Molecular Biology and Genetics and School of Biological Sciences, Seoul National University, 151-742, Seoul, Korea

    Yoontae Lee, Chiyoung Ahn, Jinju Han, Hyounjeong Choi, Jaekwang Kim, Jeongbin Yim, Sunyoung Kim & V. Narry Kim

  2. Department of Biology, Yonsei University, 120-749, Seoul, Korea

    Junho Lee

  3. Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHUL, Ste-Foy, Quebec, G1V 4G2, Canada

    Patrick Provost

  4. Department of Medical Biochemistry and Biophysics, Karolinska Institute, S-171 77, Stockholm, Sweden

    Olof Rådmark

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Correspondence to V. Narry Kim.

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Lee, Y., Ahn, C., Han, J. et al. The nuclear RNase III Drosha initiates microRNA processing. Nature 425, 415–419 (2003). https://doi.org/10.1038/nature01957

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