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The Drosha-DGCR8 complex in primary microRNA processing

Cited 1303 time in Web of Science Cited 1367 time in Scopus
Authors
Han, Jin Ju; Lee, Yoontae; Yeom, Kyu-Hyun; Kim, Young-Kook; Jin, Hua; Kim, V. Narry
Issue Date
2004-12
Citation
Genes and Development, Vol.18 No.24, pp.3016-3027
Keywords
microRNADroshaDGCR8processing
Abstract
RNase III proteins play key roles in microRNA (miRNA) biogenesis. The nuclear RNase III Drosha cleaves primary miRNAs (pri-miRNAs) to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic RNase III Dicer to generate mature miRNAs. While Dicer (class III) and other simple RNase III proteins (class I) have been studied intensively, the class II enzyme Drosha remains to be characterized. Here we dissected the action mechanism of human Drosha by generating mutants and by characterizing its new interacting partner, DGCR8. The basic action mechanism of Drosha was found to be similar to that of human Dicer; the RNase III domains A and B form an intramolecular dimer and cleave the 3' and 5' strands of the stem, respectively. Human Drosha fractionates at similar to650 kDa, indicating that Drosha functions as a large complex. In this complex, Drosha interacts with DGCR8, which contains two double-stranded RNA (dsRNA)-binding domains. By RNAi and biochemical reconstitution, we show that DGCR8 may be an essential component of the pri-miRNA processing complex, along with Drosha. Based on these results, we propose a model for the action mechanism of class II RNase III proteins.
ISSN
0890-9369
URI
http://hdl.handle.net/10371/171894
DOI
https://doi.org/10.1101/gad.1262504
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College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
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