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

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 accura...

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Autores principales: Nguyen, Tuan Anh, Park, Joha, Dang, Thi Lieu, Choi, Yeon-Gil, Kim, V Narry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009577/
https://www.ncbi.nlm.nih.gov/pubmed/29750274
http://dx.doi.org/10.1093/nar/gky248
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author Nguyen, Tuan Anh
Park, Joha
Dang, Thi Lieu
Choi, Yeon-Gil
Kim, V Narry
author_facet Nguyen, Tuan Anh
Park, Joha
Dang, Thi Lieu
Choi, Yeon-Gil
Kim, V Narry
author_sort Nguyen, Tuan Anh
collection PubMed
description 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.
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spelling pubmed-60095772018-06-25 Microprocessor depends on hemin to recognize the apical loop of primary microRNA Nguyen, Tuan Anh Park, Joha Dang, Thi Lieu Choi, Yeon-Gil Kim, V Narry Nucleic Acids Res Nucleic Acid Enzymes 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. Oxford University Press 2018-06-20 2018-05-10 /pmc/articles/PMC6009577/ /pubmed/29750274 http://dx.doi.org/10.1093/nar/gky248 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Nucleic Acid Enzymes
Nguyen, Tuan Anh
Park, Joha
Dang, Thi Lieu
Choi, Yeon-Gil
Kim, V Narry
Microprocessor depends on hemin to recognize the apical loop of primary microRNA
title Microprocessor depends on hemin to recognize the apical loop of primary microRNA
title_full Microprocessor depends on hemin to recognize the apical loop of primary microRNA
title_fullStr Microprocessor depends on hemin to recognize the apical loop of primary microRNA
title_full_unstemmed Microprocessor depends on hemin to recognize the apical loop of primary microRNA
title_short Microprocessor depends on hemin to recognize the apical loop of primary microRNA
title_sort microprocessor depends on hemin to recognize the apical loop of primary microrna
topic Nucleic Acid Enzymes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009577/
https://www.ncbi.nlm.nih.gov/pubmed/29750274
http://dx.doi.org/10.1093/nar/gky248
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