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. 2021 Feb 10;11:3476. doi: 10.1038/s41598-021-82706-2

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© The Author(s) 2021

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

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Contribution of MEF2C to miRNA regulation in differentiated muscle cells. (a) MA-plot showing the prediction of differentially expressed miRNAs between proliferating HSkM cells and myotubes after 4 days of differentiation (n = 3 HSkM_0h and n = 3 HSkM_4d). The red dots represent the statistically significant results for miRNAs downregulated; the green dots represent significantly upregulated miRNAs (P_adj < 0.05; a cutoff of a baseMean > 10). (b) Comparison of miRNA expression changes in two sets of experiments: MEF2C KD cells versus control treated cells (separately for siMEF2C_1 and siMEF2C_2) and 4 days differentiated muscle cells versus myoblasts (HSkM differentiation). Linear regression scatter plots of miRNAs log 2FC expression values were calculated by comparison of miRNAs significantly changed upon MEF2C KD (P_adj < 0.05) and miRNA significantly changed upon HSkMs differentiation (P_adj < 0.05). The statistical analysis for linear regression was done by using the GraphPad Prism 8.3.0 tool. (c) Schematic overview of MEF2C activity in muscle cells. MEF2C, as a transcription factor, can both activate (e.g., pri-miR-133a) and repress (e.g., pri-miR-376a) miRNA expression. Interaction of MEF2C within promoter of TUT4 leads to increase of TUT4 level and normal 3′-uridylation of pre-miRNAs and miRNAs. Proper dynamics of uridylation guarantee the correct turnover of short pre-miRNA fragments. Red triangles represent downregulation, and green triangles upregulation.