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Processing of primary microRNAs by the Microprocessor complex

Author

Listed:
  • Ahmet M. Denli

    (Watson School of Biological Sciences)

  • Bastiaan B. J. Tops

    (The Hubrecht Laboratory Centre for Biomedical Genetics)

  • Ronald H. A. Plasterk

    (The Hubrecht Laboratory Centre for Biomedical Genetics)

  • René F. Ketting

    (The Hubrecht Laboratory Centre for Biomedical Genetics)

  • Gregory J. Hannon

    (Watson School of Biological Sciences)

Abstract

Mature microRNAs (miRNAs) are generated via a two-step processing pathway to yield ∼22-nucleotide small RNAs that regulate gene expression at the post-transcriptional level1. Initial cleavage is catalysed by Drosha, a nuclease of the RNase III family, which acts on primary miRNA transcripts (pri-miRNAs) in the nucleus2. Here we show that Drosha exists in a multiprotein complex, the Microprocessor, and begin the process of deconstructing that complex into its constituent components. Along with Drosha, the Microprocessor also contains Pasha (partner of Drosha), a double-stranded RNA binding protein. Suppression of Pasha expression in Drosophila cells or Caenorhabditis elegans interferes with pri-miRNA processing, leading to an accumulation of pri-miRNAs and a reduction in mature miRNAs. Finally, depletion or mutation of pash-1 in C. elegans causes de-repression of a let-7 reporter and the appearance of phenotypic defects overlapping those observed upon examination of worms with lesions in Dicer (dcr-1) or Drosha (drsh-1). Considered together, these results indicate a role for Pasha in miRNA maturation and miRNA-mediated gene regulation.

Suggested Citation

  • Ahmet M. Denli & Bastiaan B. J. Tops & Ronald H. A. Plasterk & René F. Ketting & Gregory J. Hannon, 2004. "Processing of primary microRNAs by the Microprocessor complex," Nature, Nature, vol. 432(7014), pages 231-235, November.
    • Handle: RePEc:nat:nature:v:432:y:2004:i:7014:d:10.1038_nature03049
    DOI: 10.1038/nature03049
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    Cited by:

    1. Shuangmei Tian & Ziyu Zhao & Beibei Ren & Degeng Wang, 2024. "Non-Linear Relationship between MiRNA Regulatory Activity and Binding Site Counts on Target mRNAs," Data, MDPI, vol. 9(10), pages 1-13, September.

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