Processing of primary microRNAs by the Microprocessor complex.
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.
Mesh Terms:
Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cell Line, Drosophila Proteins, Drosophila melanogaster, Endoribonucleases, Genes, Reporter, Humans, MicroRNAs, Multiprotein Complexes, Phenotype, Protein Binding, Protein Structure, Tertiary, RNA Processing, Post-Transcriptional, RNA-Binding Proteins, Ribonuclease III
Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cell Line, Drosophila Proteins, Drosophila melanogaster, Endoribonucleases, Genes, Reporter, Humans, MicroRNAs, Multiprotein Complexes, Phenotype, Protein Binding, Protein Structure, Tertiary, RNA Processing, Post-Transcriptional, RNA-Binding Proteins, Ribonuclease III
Nature
Date: Nov. 11, 2004
PubMed ID: 15531879
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