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Publication : Canonical and alternate functions of the microRNA biogenesis machinery.

First Author  Chong MM Year  2010
Journal  Genes Dev Volume  24
Issue  17 Pages  1951-60
PubMed ID  20713509 Mgi Jnum  J:163823
Mgi Id  MGI:4830012 Doi  10.1101/gad.1953310
Citation  Chong MM, et al. (2010) Canonical and alternate functions of the microRNA biogenesis machinery. Genes Dev 24(17):1951-60
abstractText  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.
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