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The nuclear RNase III Drosha initiates microRNA processing

Author

Listed:
  • Yoontae Lee

    (Seoul National University)

  • Chiyoung Ahn

    (Seoul National University)

  • Jinju Han

    (Seoul National University)

  • Hyounjeong Choi

    (Seoul National University)

  • Jaekwang Kim

    (Seoul National University)

  • Jeongbin Yim

    (Seoul National University)

  • Junho Lee

    (Yonsei University)

  • Patrick Provost

    (Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHUL)

  • Olof Rådmark

    (Karolinska Institute)

  • Sunyoung Kim

    (Seoul National University)

  • V. Narry Kim

    (Seoul National University)

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.

Suggested Citation

  • Yoontae Lee & Chiyoung Ahn & Jinju Han & Hyounjeong Choi & Jaekwang Kim & Jeongbin Yim & Junho Lee & Patrick Provost & Olof Rådmark & Sunyoung Kim & V. Narry Kim, 2003. "The nuclear RNase III Drosha initiates microRNA processing," Nature, Nature, vol. 425(6956), pages 415-419, September.
  • Handle: RePEc:nat:nature:v:425:y:2003:i:6956:d:10.1038_nature01957
    DOI: 10.1038/nature01957
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    Citations

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    Cited by:

    1. Lingzi Xia & Yangwu Ren & Xue Fang & Zhihua Yin & Xuelian Li & Wei Wu & Peng Guan & Baosen Zhou, 2014. "Prognostic Role of Common MicroRNA Polymorphisms in Cancers: Evidence from a Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(10), pages 1-8, October.
    2. Bin Liu & Longyun Fang & Fule Liu & Xiaolong Wang & Junjie Chen & Kuo-Chen Chou, 2015. "Identification of Real MicroRNA Precursors with a Pseudo Structure Status Composition Approach," PLOS ONE, Public Library of Science, vol. 10(3), pages 1-20, March.
    3. Le Thi Truc Linh, 2018. "The Microrna 29 family and its regulation," HO CHI MINH CITY OPEN UNIVERSITY JOURNAL OF SCIENCE - ENGINEERING AND TECHNOLOGY, HO CHI MINH CITY OPEN UNIVERSITY JOURNAL OF SCIENCE, HO CHI MINH CITY OPEN UNIVERSITY, vol. 8(1), pages 18-27.
    4. Paola Mozzoni & Diana Poli & Silvana Pinelli & Sara Tagliaferri & Massimo Corradi & Delia Cavallo & Cinzia Lucia Ursini & Daniela Pigini, 2023. "Benzene Exposure and MicroRNAs Expression: In Vitro, In Vivo and Human Findings," IJERPH, MDPI, vol. 20(3), pages 1-16, January.
    5. Guangwen Long & Feng Wang & Quanlu Duan & Shenglan Yang & Fuqiong Chen & Wei Gong & Xu Yang & Yan Wang & Chen Chen & Dao Wen Wang, 2012. "Circulating miR-30a, miR-195 and let-7b Associated with Acute Myocardial Infarction," PLOS ONE, Public Library of Science, vol. 7(12), pages 1-8, December.
    6. Xiaorong Yang & Yanan Guo & Yane Du & Jinmei Yang & Shichao Li & Shengnan Liu & Ke Li & Dechun Zhang, 2014. "Serum MicroRNA-21 as a Diagnostic Marker for Lung Carcinoma: A Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(5), pages 1-7, May.
    7. Ying Wang & Xiushan Zheng & Zhiyong Zhang & Jinfeng Zhou & Guohong Zhao & Jianjun Yang & Limin Xia & Rui Wang & Xiqiang Cai & Hao Hu & Cailin Zhu & Yongzhan Nie & Kaichun Wu & Dexin Zhang & Daiming Fa, 2012. "MicroRNA-149 Inhibits Proliferation and Cell Cycle Progression through the Targeting of ZBTB2 in Human Gastric Cancer," PLOS ONE, Public Library of Science, vol. 7(10), pages 1-10, October.
    8. Maurizio Marrale & Nadia Ninfa Albanese & Francesco Calì & Valentino Romano, 2014. "Assessing the Impact of Copy Number Variants on miRNA Genes in Autism by Monte Carlo Simulation," PLOS ONE, Public Library of Science, vol. 9(3), pages 1-10, March.
    9. Sofia Khan & Dario Greco & Kyriaki Michailidou & Roger L Milne & Taru A Muranen & Tuomas Heikkinen & Kirsimari Aaltonen & Joe Dennis & Manjeet K Bolla & Jianjun Liu & Per Hall & Astrid Irwanto & Keith, 2014. "MicroRNA Related Polymorphisms and Breast Cancer Risk," PLOS ONE, Public Library of Science, vol. 9(11), pages 1-11, November.
    10. San-Nung Chen & Renin Chang & Li-Te Lin & Chyi-Uei Chern & Hsiao-Wen Tsai & Zhi-Hong Wen & Yi-Han Li & Chia-Jung Li & Kuan-Hao Tsui, 2019. "MicroRNA in Ovarian Cancer: Biology, Pathogenesis, and Therapeutic Opportunities," IJERPH, MDPI, vol. 16(9), pages 1-14, April.
    11. Jun Wang & Jinyong Huang & Yunlong Hu & Qianwen Guo & Shasha Zhang & Jinglin Tian & Yanqin Niu & Ling Ji & Yuzhong Xu & Peijun Tang & Yaqin He & Yuna Wang & Shuya Zhang & Hao Yang & Kang Kang & Xinchu, 2024. "Terminal modifications independent cell-free RNA sequencing enables sensitive early cancer detection and classification," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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