Denli, A. M., Tops, B. B., Plasterk, R. H., Ketting, R. F., Hannon, G. J. (November 2004) Processing of primary microRNAs by the Microprocessor complex. Nature, 432 (7014). pp. 231-5. ISSN 1476-4687 (Electronic)
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.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Animals Caenorhabditis elegans genetics metabolism Caenorhabditis elegans Proteins genetics metabolism Cell Line Drosophila Proteins chemistry genetics metabolism Drosophila melanogaster genetics metabolism Endoribonucleases genetics metabolism Genes, Reporter genetics Humans MicroRNAs genetics metabolism Multiprotein Complexes Phenotype Protein Binding Protein Structure Tertiary RNA Processing Post-Transcriptional RNA-Binding Proteins chemistry metabolism Ribonuclease III chemistry genetics metabolism |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > sRNA |
| CSHL Authors: | |
| Communities: | CSHL labs > Hannon lab School of Biological Sciences > Publications |
| Depositing User: | CSHL Librarian |
| Date: | 11 November 2004 |
| Date Deposited: | 09 Feb 2012 17:05 |
| Last Modified: | 19 Sep 2014 14:57 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/22358 |
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