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Processing of primary microRNAs by the Microprocessor complex

Nature. 2004 Nov 11;432(7014):231-5. doi: 10.1038/nature03049. Epub 2004 Nov 7.

Abstract

Mature microRNAs (miRNAs) are generated via a two-step processing pathway to yield approximately 22-nucleotide small RNAs that regulate gene expression at the post-transcriptional level. Initial cleavage is catalysed by Drosha, a nuclease of the RNase III family, which acts on primary miRNA transcripts (pri-miRNAs) in the nucleus. 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Line
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism
  • Genes, Reporter / genetics
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Multiprotein Complexes
  • Phenotype
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA Processing, Post-Transcriptional*
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism*
  • Ribonuclease III / chemistry
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Drosophila Proteins
  • MicroRNAs
  • Multiprotein Complexes
  • RNA-Binding Proteins
  • Endoribonucleases
  • dcr-1 protein, C elegans
  • Ribonuclease III
  • drosha protein, Drosophila
  • drsh-1 protein, C elegans