CRISPR/Cas9 editing reveals novel mechanisms of clustered microRNA regulation and function

Abstract MicroRNAs (miRNAs) are important regulators of diverse physiological and pathophysiological processes. MiRNA families and clusters are two key features in miRNA biology. Here we explore the use of CRISPR/Cas9 as a powerful tool to delineate the function and regulation of miRNA families and...

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Autores principales:	Lazaros Lataniotis, Andreas Albrecht, Fatma O. Kok, Clinton A. L. Monfries, Lorena Benedetti, Nathan D. Lawson, Simon M. Hughes, Kathleen Steinhofel, Manuel Mayr, Anna Zampetaki
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c6f1f4ed873b4bfc9c27edba831e3e8f
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spelling	oai:doaj.org-article:c6f1f4ed873b4bfc9c27edba831e3e8f2021-12-02T16:06:41ZCRISPR/Cas9 editing reveals novel mechanisms of clustered microRNA regulation and function10.1038/s41598-017-09268-02045-2322https://doaj.org/article/c6f1f4ed873b4bfc9c27edba831e3e8f2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09268-0https://doaj.org/toc/2045-2322Abstract MicroRNAs (miRNAs) are important regulators of diverse physiological and pathophysiological processes. MiRNA families and clusters are two key features in miRNA biology. Here we explore the use of CRISPR/Cas9 as a powerful tool to delineate the function and regulation of miRNA families and clusters. We focused on four miRNA clusters composed of miRNA members of the same family, homo-clusters or different families, hetero-clusters. Our results highlight different regulatory mechanisms in miRNA cluster expression. In the case of the miR-497~195 cluster, editing of miR-195 led to a significant decrease in the expression of the other miRNA in the cluster, miR-497a. Although no gene editing was detected in the miR-497a genomic locus, computational simulation revealed alteration in the three dimensional structure of the pri-miR-497~195 that may affect its processing. In cluster miR-143~145 our results imply a feed-forward regulation, although structural changes cannot be ruled out. Furthermore, in the miR-17~92 and miR-106~25 clusters no interdependency in miRNA expression was observed. Our findings suggest that CRISPR/Cas9 is a powerful gene editing tool that can uncover novel mechanisms of clustered miRNA regulation and function.Lazaros LataniotisAndreas AlbrechtFatma O. KokClinton A. L. MonfriesLorena BenedettiNathan D. LawsonSimon M. HughesKathleen SteinhofelManuel MayrAnna ZampetakiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lazaros Lataniotis Andreas Albrecht Fatma O. Kok Clinton A. L. Monfries Lorena Benedetti Nathan D. Lawson Simon M. Hughes Kathleen Steinhofel Manuel Mayr Anna Zampetaki CRISPR/Cas9 editing reveals novel mechanisms of clustered microRNA regulation and function
description	Abstract MicroRNAs (miRNAs) are important regulators of diverse physiological and pathophysiological processes. MiRNA families and clusters are two key features in miRNA biology. Here we explore the use of CRISPR/Cas9 as a powerful tool to delineate the function and regulation of miRNA families and clusters. We focused on four miRNA clusters composed of miRNA members of the same family, homo-clusters or different families, hetero-clusters. Our results highlight different regulatory mechanisms in miRNA cluster expression. In the case of the miR-497~195 cluster, editing of miR-195 led to a significant decrease in the expression of the other miRNA in the cluster, miR-497a. Although no gene editing was detected in the miR-497a genomic locus, computational simulation revealed alteration in the three dimensional structure of the pri-miR-497~195 that may affect its processing. In cluster miR-143~145 our results imply a feed-forward regulation, although structural changes cannot be ruled out. Furthermore, in the miR-17~92 and miR-106~25 clusters no interdependency in miRNA expression was observed. Our findings suggest that CRISPR/Cas9 is a powerful gene editing tool that can uncover novel mechanisms of clustered miRNA regulation and function.
format	article
author	Lazaros Lataniotis Andreas Albrecht Fatma O. Kok Clinton A. L. Monfries Lorena Benedetti Nathan D. Lawson Simon M. Hughes Kathleen Steinhofel Manuel Mayr Anna Zampetaki
author_facet	Lazaros Lataniotis Andreas Albrecht Fatma O. Kok Clinton A. L. Monfries Lorena Benedetti Nathan D. Lawson Simon M. Hughes Kathleen Steinhofel Manuel Mayr Anna Zampetaki
author_sort	Lazaros Lataniotis
title	CRISPR/Cas9 editing reveals novel mechanisms of clustered microRNA regulation and function
title_short	CRISPR/Cas9 editing reveals novel mechanisms of clustered microRNA regulation and function
title_full	CRISPR/Cas9 editing reveals novel mechanisms of clustered microRNA regulation and function
title_fullStr	CRISPR/Cas9 editing reveals novel mechanisms of clustered microRNA regulation and function
title_full_unstemmed	CRISPR/Cas9 editing reveals novel mechanisms of clustered microRNA regulation and function
title_sort	crispr/cas9 editing reveals novel mechanisms of clustered microrna regulation and function
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c6f1f4ed873b4bfc9c27edba831e3e8f
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CRISPR/Cas9 editing reveals novel mechanisms of clustered microRNA regulation and function

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