Department of Molecular, Cell, and Cancer Biology
Genetics and Genomics | Investigative Techniques | Nucleic Acids, Nucleotides, and Nucleosides
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.
Genetic engineering, miRNAs
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Copyright © 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/.
DOI of Published Version
Sci Rep. 2017 Aug 17;7(1):8585. doi: 10.1038/s41598-017-09268-0. Link to article on publisher's site
Lataniotis, Lazaros; Albrecht, Andreas; Kok, Fatma O.; Monfries, Clinton A. L.; Benedetti, Lorena; Lawson, Nathan D.; Hughes, Simon M.; Steinhofel, Kathleen; Mayr, Manuel; and Zampetaki, Anna, "CRISPR/Cas9 editing reveals novel mechanisms of clustered microRNA regulation and function" (2017). Open Access Articles. 3244.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.