MEF2C shapes the microtranscriptome during differentiation of skeletal muscles.
MEF2C shapes the microtranscriptome during differentiation of skeletal muscles.
复制标题
DOI：
10.1038/s41598-021-82706-2
复制
发表时间：
2021-02-10
影响因子：
4.6
通讯作者：
Sobczak K
中科院分区：
文献类型：
--
作者：
Piasecka A;Sekrecki M;Szcześniak MW;Sobczak K
肌细胞增强因子 2C (MEF2C) 是一种调节心脏和骨骼肌分化和生长的转录因子。一些蛋白质编码基因被确定为该因子的目标；然而，人们对其对微转录组组成和生肌程序动态的贡献知之甚少。在本报告中，我们旨在解决这个问题。对人类肌肉细胞小 RNA 的深度测序揭示了一组对 MEF2C 耗竭敏感的 microRNA (miRNA)，包括几种肌肉特异性 miRNA。正如预期的那样，在 MEF2C 敲低的细胞中，我们发现大部分 miRNA 下调；然而，多达三分之一的改变的 miRNA 被上调。这些变化大部分是由转录效率驱动的。此外，我们发现 MEF2C 影响 miRNA 的非模板 3' 端核苷酸添加，主要是寡尿苷化。这些修饰的速率与介导 RNA 3'-尿苷化的 TUT4 水平相关。最后，我们发现四分之一在人类骨骼肌成肌细胞分化时发生显着变化的 miRNA 在 MEF2C 缺陷细胞中发生相反改变。我们得出结论，MEF2C 是调节微转录组数量和质量的重要因素，在肌肉细胞分化过程中对许多 miRNA 的稳定性和特异性留下了印记。
Myocyte enhancer factor 2C (MEF2C) is a transcription factor that regulates heart and skeletal muscle differentiation and growth. Several protein-encoding genes were identified as targets of this factor; however, little is known about its contribution to the microtranscriptome composition and dynamics in myogenic programs. In this report, we aimed to address this question. Deep sequencing of small RNAs of human muscle cells revealed a set of microRNAs (miRNAs), including several muscle-specific miRNAs, that are sensitive to MEF2C depletion. As expected, in cells with knockdown of MEF2C, we found mostly downregulated miRNAs; nevertheless, as much as one-third of altered miRNAs were upregulated. The majority of these changes are driven by transcription efficiency. Moreover, we found that MEF2C affects nontemplated 3′-end nucleotide addition of miRNAs, mainly oligouridylation. The rate of these modifications is associated with the level of TUT4 which mediates RNA 3′-uridylation. Finally, we found that a quarter of miRNAs which significantly changed upon differentiation of human skeletal myoblasts is inversely altered in MEF2C deficient cells. We concluded that MEF2C is an essential factor regulating both the quantity and quality of the microtranscriptome, leaving an imprint on the stability and perhaps specificity of many miRNAs during the differentiation of muscle cells.
登录
查看更多内容
影响因子：
4.5
作者：
Lee, Dooyoung;Park, Daechan;Shin, Chanseok
通讯作者：
Shin, Chanseok
影响因子：
7
作者：
Kingston, Elena R.;Bartel, David P.
通讯作者：
Bartel, David P.
DOI：
10.1261/rna.060095.116
发表时间：
2017-06
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Gutiérrez-Vázquez C;Enright AJ;Rodríguez-Galán A;Pérez-García A;Collier P;Jones MR;Benes V;Mizgerd JP;Mittelbrunn M;Ramiro AR;Sánchez-Madrid F
通讯作者：
Sánchez-Madrid F
影响因子：
2.1
作者：
Ab Hakim, Nor Hakimah;Kounishi, Toshiki;Suzuki, Hitoshi
通讯作者：
Suzuki, Hitoshi
DOI：
10.1073/pnas.0710558105
发表时间：
2007-12-26
影响因子：
11.1
作者：
Liu, Ning;Williams, Andrew H.;Olson, Eric N.
通讯作者：
Olson, Eric N.