Processing of primary microRNAs by the Microprocessor complex

Ahmet M. Denli, Bastiaan B. J. Tops, Ronald H. A. Plasterk, René F. Ketting and Gregory J. Hannon ()
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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

Nature, 2004, vol. 432, issue 7014, 231-235

Abstract: 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.

Date: 2004
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DOI: 10.1038/nature03049

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