1. The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA
2. These authors contributed equally to this work

Correspondence to: Ramin Shiekhattar¹ Email: shiekhattar@wistar.upenn.edu

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^{1, 2}, haematopoietic lineage differentiation in mammals³, neuronal patterning in nematodes⁴ and leaf and flower development in plants^{5, 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.

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