Molecular Basis for the Single-Nucleotide Precision of Primary microRNA Processing
- Authors
- Kwon, S. Chul; Baek, S. Chan; Choi, Yeon-Gil; Yang, Jihye; Lee, Young-suk; Woo, Jae-Sung; Kim, V. Narry
- Issue Date
- 7-Feb-2019
- Publisher
- CELL PRESS
- Keywords
- DGCR8; DROSHA; microRNA; miRNA; RNase III
- Citation
- MOLECULAR CELL, v.73, no.3, pp.505 - +
- Indexed
- SCIE
SCOPUS
- Journal Title
- MOLECULAR CELL
- Volume
- 73
- Number
- 3
- Start Page
- 505
- End Page
- +
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/67651
- DOI
- 10.1016/j.molcel.2018.11.005
- ISSN
- 1097-2765
- 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 similar to 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.
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