Heme enables proper positioning of Drosha and DGCR8 on primary microRNAs

MicroRNAs regulate the expression of many proteins and require specific maturation steps. Primary microRNA transcripts (pri-miRs) are cleaved by Microprocessor, a complex containing the RNase Drosha and its partner protein, DGCR8. Although DGCR8 is known to bind heme, the molecular role of heme in p...

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Autores principales: Partin, Alexander C., Ngo, Tri D., Herrell, Emily, Jeong, Byung-Cheon, Hon, Gary, Nam, Yunsun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700927/
https://www.ncbi.nlm.nih.gov/pubmed/29170488
http://dx.doi.org/10.1038/s41467-017-01713-y
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author Partin, Alexander C.
Ngo, Tri D.
Herrell, Emily
Jeong, Byung-Cheon
Hon, Gary
Nam, Yunsun
author_facet Partin, Alexander C.
Ngo, Tri D.
Herrell, Emily
Jeong, Byung-Cheon
Hon, Gary
Nam, Yunsun
author_sort Partin, Alexander C.
collection PubMed
description MicroRNAs regulate the expression of many proteins and require specific maturation steps. Primary microRNA transcripts (pri-miRs) are cleaved by Microprocessor, a complex containing the RNase Drosha and its partner protein, DGCR8. Although DGCR8 is known to bind heme, the molecular role of heme in pri-miR processing is unknown. Here we show that heme is critical for Microprocessor to process pri-miRs with high fidelity. Furthermore, the degree of inherent heme dependence varies for different pri-miRs. Heme-dependent pri-miRs fail to properly recruit Drosha, but heme-bound DGCR8 can correct erroneous binding events. Rather than changing the oligomerization state, heme induces a conformational change in DGCR8. Finally, we demonstrate that heme activates DGCR8 to recognize pri-miRs by specifically binding the terminal loop near the 3′ single-stranded segment.
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spelling pubmed-57009272017-11-27 Heme enables proper positioning of Drosha and DGCR8 on primary microRNAs Partin, Alexander C. Ngo, Tri D. Herrell, Emily Jeong, Byung-Cheon Hon, Gary Nam, Yunsun Nat Commun Article MicroRNAs regulate the expression of many proteins and require specific maturation steps. Primary microRNA transcripts (pri-miRs) are cleaved by Microprocessor, a complex containing the RNase Drosha and its partner protein, DGCR8. Although DGCR8 is known to bind heme, the molecular role of heme in pri-miR processing is unknown. Here we show that heme is critical for Microprocessor to process pri-miRs with high fidelity. Furthermore, the degree of inherent heme dependence varies for different pri-miRs. Heme-dependent pri-miRs fail to properly recruit Drosha, but heme-bound DGCR8 can correct erroneous binding events. Rather than changing the oligomerization state, heme induces a conformational change in DGCR8. Finally, we demonstrate that heme activates DGCR8 to recognize pri-miRs by specifically binding the terminal loop near the 3′ single-stranded segment. Nature Publishing Group UK 2017-11-23 /pmc/articles/PMC5700927/ /pubmed/29170488 http://dx.doi.org/10.1038/s41467-017-01713-y Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Partin, Alexander C.
Ngo, Tri D.
Herrell, Emily
Jeong, Byung-Cheon
Hon, Gary
Nam, Yunsun
Heme enables proper positioning of Drosha and DGCR8 on primary microRNAs
title Heme enables proper positioning of Drosha and DGCR8 on primary microRNAs
title_full Heme enables proper positioning of Drosha and DGCR8 on primary microRNAs
title_fullStr Heme enables proper positioning of Drosha and DGCR8 on primary microRNAs
title_full_unstemmed Heme enables proper positioning of Drosha and DGCR8 on primary microRNAs
title_short Heme enables proper positioning of Drosha and DGCR8 on primary microRNAs
title_sort heme enables proper positioning of drosha and dgcr8 on primary micrornas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700927/
https://www.ncbi.nlm.nih.gov/pubmed/29170488
http://dx.doi.org/10.1038/s41467-017-01713-y
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