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PMID:15531879

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Citation

Denli, AM, Tops, BB, Plasterk, RH, Ketting, RF and Hannon, GJ (2004) Processing of primary microRNAs by the Microprocessor complex. Nature 432:231-5

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.

Links

PubMed Online version:10.1038/nature03049

Keywords

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

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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