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Microprocessor depends on hemin to recognize the apical loop of primary microRNA

Cited 26 time in Web of Science Cited 27 time in Scopus
Authors
Tuan Anh Nguyen; Park, Joha; Thi Lieu Dang; Choi, Yeon-Gil; Kim, V. Narry
Issue Date
2018-06
Citation
Nucleic Acids Research, Vol.46 No.11, pp.5726-5736
Abstract
Microprocessor, which consists of a ribonuclease III DROSHA and its cofactor DGCR8, initiates microRNA (miRNA) maturation by cleaving primary miRNA transcripts (pri-miRNAs). We recently demonstrated that the DGCR8 dimer recognizes the apical elements of pri-miRNAs, including the UGU motif, to accurately locate and orient Microprocessor on pri-miRNAs. However, the mechanism underlying the selective RNA binding remains unknown. In this study, we find that hemin, a ferric ion-containing porphyrin, enhances the specific interaction between the apical UGU motif and the DGCR8 dimer, allowing Microprocessor to achieve high efficiency and fidelity of pri-miRNA processing in vitro. Furthermore, by generating a DGCR8 mutant cell line and carrying out rescue experiments, we discover that hemin preferentially stimulates the expression of miRNAs possessing the UGU motif, thereby conferring differential regulation of miRNA maturation. Our findings reveal the molecular action mechanism of hemin in pri-miRNA processing and establish a novel function of hemin in inducing specific RNA-protein interaction.
ISSN
0305-1048
URI
https://hdl.handle.net/10371/171951
DOI
https://doi.org/10.1093/nar/gky248
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College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
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