Molecular Basis for the Single-Nucleotide Precision of Primary microRNA Processing

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Title
Molecular Basis for the Single-Nucleotide Precision of Primary microRNA Processing
Author(s)
S. Chul Kwon; S. Chan Baek; Yeon-Gil Choi; Jihye Yang; Young-suk Lee; Jae-Sung Woo; V. Narry Kim
Publication Date
2019-02
Journal
MOLECULAR CELL, v.73, no.3, pp.505 - 518.e5
Publisher
CELL PRESS
Abstract
Microprocessor, composed of DROSHA and its cofactor DGCR8, initiates microRNA (miRNA) biogenesis by processing the primary transcripts of miRNA (pri-miRNAs). Here we investigate the mechanism by which Microprocessor selects the cleavage site with single-nucleotide precision, which is crucial for the specificity and functionality of miRNAs. By testing ∼40,000 pri-miRNA variants, we find that for some pri-miRNAs the cleavage site is dictated mainly by the mGHG motif embedded in the lower stem region of pri-miRNA. Structural modeling and deep-sequencing-based complementation experiments show that the double-stranded RNA-binding domain (dsRBD) of DROSHA recognizes mGHG to place the catalytic center in the appropriate position. The mGHG motif as well as the mGHG-recognizing residues in DROSHA dsRBD are conserved across eumetazoans, suggesting that this mechanism emerged in an early ancestor of the animal lineage. Our findings provide a basis for the understanding of miRNA biogenesis and rational design of accurate small-RNA-based gene silencing. © 2018 Elsevier Inc.Target specificity of microRNA is determined by DROSHA cleavage sites. Kwon et al. show how DROSHA precisely selects the cleavage sites using the interaction between its double-stranded RNA-binding domain (dsRBD) and the mGHG motif of the primary microRNA. © 2018 Elsevier Inc.
URI
https://pr.ibs.re.kr/handle/8788114/5704
ISSN
1097-2765
Appears in Collections:
Center for RNA Research(RNA 연구단) > Journal Papers (저널논문)
Files in This Item:
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