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Allosteric regulation of noncoding RNA function by microRNAs

HSUR1 and HSUR2, two noncoding RNAs expressed by the oncogenic Herpesvirus saimiri, bind host microRNAs miR-142-3p, miR-16, and miR-27 with different purposes. While binding of miR-27 to HSUR1 triggers the degradation of the microRNA, miR-16 is tethered by HSUR2 to target host mRNAs to repress their...

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Autores principales: Gorbea, Carlos, Elhakiem, Abdalla, Cazalla, Demián
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226524/
https://www.ncbi.nlm.nih.gov/pubmed/35648438
http://dx.doi.org/10.1093/nar/gkac443
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author Gorbea, Carlos
Elhakiem, Abdalla
Cazalla, Demián
author_facet Gorbea, Carlos
Elhakiem, Abdalla
Cazalla, Demián
author_sort Gorbea, Carlos
collection PubMed
description HSUR1 and HSUR2, two noncoding RNAs expressed by the oncogenic Herpesvirus saimiri, bind host microRNAs miR-142-3p, miR-16, and miR-27 with different purposes. While binding of miR-27 to HSUR1 triggers the degradation of the microRNA, miR-16 is tethered by HSUR2 to target host mRNAs to repress their expression. Here we show that the interaction with miR-142-3p is required for the activity of both HSURs. Coimmunoprecipitation experiments revealed that miR-142-3p allosterically regulates the binding of miR-27 and miR-16 to HSUR1 and HSUR2, respectively. The binding of two different miRNAs to each HSUR is not cooperative. HSURs can be engineered to be regulated by other miRNAs, indicating that the identity of the binding miRNA is not important for HSUR regulation. Our results uncover a mechanism for allosteric regulation of noncoding RNA function and a previously unappreciated way in which microRNAs can regulate gene expression.
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spelling pubmed-92265242022-06-28 Allosteric regulation of noncoding RNA function by microRNAs Gorbea, Carlos Elhakiem, Abdalla Cazalla, Demián Nucleic Acids Res RNA and RNA-protein complexes HSUR1 and HSUR2, two noncoding RNAs expressed by the oncogenic Herpesvirus saimiri, bind host microRNAs miR-142-3p, miR-16, and miR-27 with different purposes. While binding of miR-27 to HSUR1 triggers the degradation of the microRNA, miR-16 is tethered by HSUR2 to target host mRNAs to repress their expression. Here we show that the interaction with miR-142-3p is required for the activity of both HSURs. Coimmunoprecipitation experiments revealed that miR-142-3p allosterically regulates the binding of miR-27 and miR-16 to HSUR1 and HSUR2, respectively. The binding of two different miRNAs to each HSUR is not cooperative. HSURs can be engineered to be regulated by other miRNAs, indicating that the identity of the binding miRNA is not important for HSUR regulation. Our results uncover a mechanism for allosteric regulation of noncoding RNA function and a previously unappreciated way in which microRNAs can regulate gene expression. Oxford University Press 2022-06-01 /pmc/articles/PMC9226524/ /pubmed/35648438 http://dx.doi.org/10.1093/nar/gkac443 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle RNA and RNA-protein complexes
Gorbea, Carlos
Elhakiem, Abdalla
Cazalla, Demián
Allosteric regulation of noncoding RNA function by microRNAs
title Allosteric regulation of noncoding RNA function by microRNAs
title_full Allosteric regulation of noncoding RNA function by microRNAs
title_fullStr Allosteric regulation of noncoding RNA function by microRNAs
title_full_unstemmed Allosteric regulation of noncoding RNA function by microRNAs
title_short Allosteric regulation of noncoding RNA function by microRNAs
title_sort allosteric regulation of noncoding rna function by micrornas
topic RNA and RNA-protein complexes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226524/
https://www.ncbi.nlm.nih.gov/pubmed/35648438
http://dx.doi.org/10.1093/nar/gkac443
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