The Microprocessor complex mediates the genesis of microRNAs

Richard I. Gregory, Kai-ping Yan, Govindasamy Amuthan, Thimmaiah Chendrimada, Behzad Doratotaj, Neil Cooch and Ramin Shiekhattar ()
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Richard I. Gregory: The Wistar Institute
Kai-ping Yan: The Wistar Institute
Govindasamy Amuthan: The Wistar Institute
Thimmaiah Chendrimada: The Wistar Institute
Behzad Doratotaj: The Wistar Institute
Neil Cooch: The Wistar Institute
Ramin Shiekhattar: The Wistar Institute

Nature, 2004, vol. 432, issue 7014, 235-240

Abstract: Abstract MicroRNAs (miRNAs) are a growing family of small non-protein-coding regulatory genes that regulate the expression of homologous target-gene transcripts. They have been implicated in the control of cell death and proliferation in flies1,2, haematopoietic lineage differentiation in mammals3, neuronal patterning in nematodes4 and leaf and flower development in plants5,6,7,8. miRNAs are processed by the RNA-mediated interference machinery. Drosha is an RNase III enzyme that was recently implicated in miRNA processing. Here we show that human Drosha is a component of two multi-protein complexes. The larger complex contains multiple classes of RNA-associated proteins including RNA helicases, proteins that bind double-stranded RNA, novel heterogeneous nuclear ribonucleoproteins and the Ewing's sarcoma family of proteins. The smaller complex is composed of Drosha and the double-stranded-RNA-binding protein, DGCR8, the product of a gene deleted in DiGeorge syndrome. In vivo knock-down and in vitro reconstitution studies revealed that both components of this smaller complex, termed Microprocessor, are necessary and sufficient in mediating the genesis of miRNAs from the primary miRNA transcript.

Date: 2004
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DOI: 10.1038/nature03120

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