Reference - Detail
RRC ID | 425 |
---|---|
Author | Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ. |
Title | Processing of primary microRNAs by the Microprocessor complex. |
Journal | Nature |
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. |
Volume | 432(7014) |
Pages | 231-5 |
Published | 2004-11-11 |
DOI | 10.1038/nature03049 |
PII | nature03049 |
PMID | 15531879 |
MeSH | 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* |
IF | 42.779 |
Times Cited | 1542 |
WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
Resource | |
C.elegans | tm0654 |