Canonical and alternate functions of the microRNA biogenesis machinery

Chong, M. M. W., Zhang, G. A., Cheloufi, S., Neubert, T. A., Hannon, G. J., Littman, D. R. (September 2010) Canonical and alternate functions of the microRNA biogenesis machinery. Genes & Development, 24 (17). pp. 1951-1960. ISSN 0890-9369

URL: http://www.ncbi.nlm.nih.gov/pubmed/20713509
DOI: 10.1101/gad.1953310

Abstract

The canonical microRNA (miRNA) biogenesis pathway requires two RNaseIII enzymes: Drosha and Dicer. To understand their functions in mammals in vivo, we engineered mice with germline or tissue-specific inactivation of the genes encoding these two proteins. Changes in proteomic and transcriptional profiles that were shared in Dicer-and Drosha-deficient mice confirmed the requirement for both enzymes in canonical miRNA biogenesis. However, deficiency in Drosha or Dicer did not always result in identical phenotypes, suggesting additional functions. We found that, in early-stage thymocytes, Drosha recognizes and directly cleaves many protein-coding messenger RNAs (mRNAs) with secondary stem-loop structures. In addition, we identified a subset of miRNAs generated by a Dicer-dependent but Drosha-independent mechanism. These were distinct from previously described mirtrons. Thus, in mammalian cells, Dicer is required for the biogenesis of multiple classes of miRNAs. Together, these findings extend the range of function of RNaseIII enzymes beyond canonical miRNA biogenesis, and help explain the nonoverlapping phenotypes caused by Drosha and Dicer deficiency.

Item Type: Paper
Uncontrolled Keywords: RNaseIII enzymes microRNA targets microRNA processing endonucleolytic cleavage EMBRYONIC STEM-CELLS MICROPROCESSOR COMPLEX DROSHA-DGCR8 COMPLEX REGULATORY RNAS MOUSE OOCYTES WEB SERVER DICER IDENTIFICATION PREDICTION PATHWAY
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
bioinformatics > genomics and proteomics > annotation > gene expression profiling annotation
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

organism description > animal > mammal > rodent > mouse
therapies > stem cells
CSHL Authors:
Communities: CSHL Cancer Center Shared Resources > Bioinformatics Service
CSHL Cancer Center Shared Resources > DNA Sequencing Service
CSHL labs > Hannon lab
CSHL Cancer Center Program > Cancer Genetics
Depositing User: CSHL Librarian
Date: September 2010
Date Deposited: 29 Sep 2011 14:00
Last Modified: 13 Oct 2015 19:54
PMCID: PMC2932976
Related URLs:
URI: http://repository.cshl.edu/id/eprint/15389

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