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

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dc.contributor.authorKwon, S. Chulko
dc.contributor.authorBaek, S. Chanko
dc.contributor.authorChoi, Yeon-Gilko
dc.contributor.authorYang, Jihyeko
dc.contributor.authorLee, Young-sukko
dc.contributor.authorWoo, Jae-Sungko
dc.contributor.authorKim, V. Narryko
dc.date.accessioned2021-02-01T01:10:15Z-
dc.date.available2021-02-01T01:10:15Z-
dc.date.created2021-02-01-
dc.date.issued2019-02-
dc.identifier.citationMOLECULAR CELL, v.73, no.3, pp.505 - +-
dc.identifier.issn1097-2765-
dc.identifier.urihttp://hdl.handle.net/10203/280415-
dc.description.abstractMicroprocessor, 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.-
dc.languageEnglish-
dc.publisherCELL PRESS-
dc.titleMolecular Basis for the Single-Nucleotide Precision of Primary microRNA Processing-
dc.typeArticle-
dc.identifier.wosid000458015200011-
dc.identifier.scopusid2-s2.0-85061010954-
dc.type.rimsART-
dc.citation.volume73-
dc.citation.issue3-
dc.citation.beginningpage505-
dc.citation.endingpage+-
dc.citation.publicationnameMOLECULAR CELL-
dc.identifier.doi10.1016/j.molcel.2018.11.005-
dc.contributor.localauthorLee, Young-suk-
dc.contributor.nonIdAuthorKwon, S. Chul-
dc.contributor.nonIdAuthorBaek, S. Chan-
dc.contributor.nonIdAuthorChoi, Yeon-Gil-
dc.contributor.nonIdAuthorYang, Jihye-
dc.contributor.nonIdAuthorWoo, Jae-Sung-
dc.contributor.nonIdAuthorKim, V. Narry-
dc.description.isOpenAccessN-
dc.type.journalArticleArticle-
dc.subject.keywordPlusRNA-INTERFERENCE-
dc.subject.keywordPlusRIBONUCLEASE-III-
dc.subject.keywordPlusSEQUENCE DETERMINANTS-
dc.subject.keywordPlusREAD ALIGNMENT-
dc.subject.keywordPlusDICER-
dc.subject.keywordPlusDROSHA-
dc.subject.keywordPlusRECOGNITION-
dc.subject.keywordPlusCLEAVAGE-
dc.subject.keywordPlusCOMPLEX-
dc.subject.keywordPlusPRECURSORS-
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