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Functional anatomy of the human microprocessor

Cited 270 time in Web of Science Cited 280 time in Scopus
Authors

Tuan Anh Nguyen; Jo, Myung Hyun; Choi, Yeon-Gil; Park, Joha; Kwon, S. Chul; Hohng, Sungchul; Kim, V. Narry; Woo, Jae-Sung

Issue Date
2015-06
Publisher
Cell Press
Citation
Cell, Vol.161 No.6, pp.1374-1387
Abstract
MicroRNA (miRNA) maturation is initiated by Microprocessor composed of RNase III DROSHA and its cofactor DGCR8, whose fidelity is critical for generation of functional miRNAs. To understand how Microprocessor recognizes pri-miRNAs, we here reconstitute human Microprocessor with purified recombinant proteins. We find that Microprocessor is an similar to 364 kDa heterotrimeric complex of one DROSHA and two DGCR8 molecules. Together with a 23-amino acid peptide from DGCR8, DROSHA constitutes a minimal functional core. DROSHA serves as a "ruler'' by measuring 11 bp from the basal ssRNA-dsRNA junction. DGCR8 interacts with the stem and apical elements through its dsRNA-binding domains and RNA-binding heme domain, respectively, allowing efficient and accurate processing. DROSHA and DGCR8, respectively, recognize the basal UG and apical UGU motifs, which ensure proper orientation of the complex. These findings clarify controversies over the action mechanism of DROSHA and allow us to build a general model for pri-miRNA processing.
ISSN
0092-8674
URI
https://hdl.handle.net/10371/171957
DOI
https://doi.org/10.1016/j.cell.2015.05.010
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  • College of Natural Sciences
  • School of Biological Sciences
Research Area Molecular Biology & Genetics

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