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Functional anatomy of the human microprocessor

Cited 104 time in webofscience Cited 108 time in scopus
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Title
Functional anatomy of the human microprocessor
Author(s)
Tuan Anh Nguyen; Jo M.H.; Yeon-Gil Choi; Joha Park; S. Chul Kwon; Hohng S.; V. Narry Kim; Jae-Sung Woo
Publication Date
2015-06
Journal
CELL, v.161, no.6, pp.1374 - 1387
Publisher
CELL PRESS
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 ∼ 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. © 2015 Elsevier Inc
URI
https://pr.ibs.re.kr/handle/8788114/1665
ISSN
0092-8674
Appears in Collections:
Center for RNA Research(RNA 연구단) > Journal Papers (저널논문)
Files in This Item:
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