The Microprocessor complex mediates the genesis of microRNAs

Richard I. Gregory, Kai Ping Yan, Govindasamy Amuthan, Thimmalah Chendrimada, Behzad Doratotaj, Neil Cooch, Ramin Shiekhattar

Research output: Contribution to journalArticle

1833 Scopus citations

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 flies, haematopoietic lineage differentiation in mammals, neuronal patterning in nematodes and leaf and flower development in plants. 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.

Original languageEnglish (US)
Pages (from-to)235-240
Number of pages6
JournalNature
Volume432
Issue number7014
DOIs
StatePublished - Nov 11 2004
Externally publishedYes

ASJC Scopus subject areas

  • General

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    Gregory, R. I., Yan, K. P., Amuthan, G., Chendrimada, T., Doratotaj, B., Cooch, N., & Shiekhattar, R. (2004). The Microprocessor complex mediates the genesis of microRNAs. Nature, 432(7014), 235-240. https://doi.org/10.1038/nature03120