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

Lataniotis, Lazaros, Albrecht, Andreas A., Kok, Fatma O., Monfries, Clinton A. L., Benedetti, Lorena, Lawson, Nathan D., Hughes, Simon M., Steinhofel, Kathleen, Mayr, Manuel and Zampetaki, Anna (2017) Crispr/Cas9 editing reveals novel mechanisms of clustered microRNA regulation and function. Scientific Reports, 7 , 8585. pp. 1-14. ISSN 2045-2322 [Article] (doi:10.1038/s41598-017-09268-0)

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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, homoclusters 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.

Item Type: Article
Additional Information: Article number = 8585
Research Areas: A. > School of Science and Technology > Computer Science
Item ID: 22359
Notes on copyright: © Te 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/
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Depositing User: Andreas Albrecht
Date Deposited: 17 Aug 2017 15:48
Last Modified: 12 Jun 2021 14:00
URI: https://eprints.mdx.ac.uk/id/eprint/22359

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