Molecular Basis for the Single-Nucleotide Precision of Primary microRNA Processing
DC Field | Value | Language |
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dc.contributor.author | S. Chul Kwon | - |
dc.contributor.author | S. Chan Baek | - |
dc.contributor.author | Yeon-Gil Choi | - |
dc.contributor.author | Jihye Yang | - |
dc.contributor.author | Young-suk Lee | - |
dc.contributor.author | Jae-Sung Woo | - |
dc.contributor.author | V. Narry Kim | - |
dc.date.available | 2019-05-02T08:08:46Z | - |
dc.date.created | 2019-02-18 | - |
dc.date.issued | 2019-02 | - |
dc.identifier.issn | 1097-2765 | - |
dc.identifier.uri | https://pr.ibs.re.kr/handle/8788114/5704 | - |
dc.description.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. | - |
dc.description.uri | 1 | - |
dc.language | 영어 | - |
dc.publisher | CELL PRESS | - |
dc.subject | DGCR8 | - |
dc.subject | DROSHA | - |
dc.subject | microRNA | - |
dc.subject | miRNA | - |
dc.subject | RNase III | - |
dc.title | Molecular Basis for the Single-Nucleotide Precision of Primary microRNA Processing | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.identifier.wosid | 000458015200011 | - |
dc.identifier.scopusid | 2-s2.0-85061010954 | - |
dc.identifier.rimsid | 67019 | - |
dc.contributor.affiliatedAuthor | S. Chul Kwon | - |
dc.contributor.affiliatedAuthor | S. Chan Baek | - |
dc.contributor.affiliatedAuthor | Yeon-Gil Choi | - |
dc.contributor.affiliatedAuthor | Jihye Yang | - |
dc.contributor.affiliatedAuthor | Young-suk Lee | - |
dc.contributor.affiliatedAuthor | Jae-Sung Woo | - |
dc.contributor.affiliatedAuthor | V. Narry Kim | - |
dc.identifier.doi | 10.1016/j.molcel.2018.11.005 | - |
dc.identifier.bibliographicCitation | MOLECULAR CELL, v.73, no.3, pp.505 - 518.e5 | - |
dc.citation.title | MOLECULAR CELL | - |
dc.citation.volume | 73 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 505 | - |
dc.citation.endPage | 518.e5 | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordAuthor | DGCR8 | - |
dc.subject.keywordAuthor | DROSHA | - |
dc.subject.keywordAuthor | microRNA | - |
dc.subject.keywordAuthor | miRNA | - |
dc.subject.keywordAuthor | RNase III | - |