SRSF10 Plays a Role in Myoblast Differentiation and Glucose Production via Regulation of Alternative Splicing
SRSF10 Plays a Role in Myoblast Differentiation and Glucose Production via Regulation of Alternative Splicing
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SRSF10 通过选择性剪接的调节在成肌细胞分化和葡萄糖生产中发挥作用
DOI：
10.1016/j.celrep.2015.10.038
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发表时间：
2015-11-24
期刊：
影响因子：
8.8
通讯作者：
Feng, Ying
中科院分区：
文献类型：
--
作者：
Wei, Ning;Cheng, Yuanming;Feng, Ying
选择性剪接是控制高等真核生物基因表达和蛋白质多样性的主要机制。我们报告了剪接因子SRSF10在横纹肌发育、成肌细胞分化以及细胞和小鼠葡萄糖产生过程中的作用。RNA测序和分子分析的结合使我们能够确定SRSF10控制的肌肉特异剪接事件，这些剪接事件在横纹肌发育中起关键作用。包含Lrrfip1的第16和17外显子是一种肌肉特异性事件，由SRSF10激活，对成肌细胞的分化至关重要。另一方面，在小鼠原代肝细胞中，PGC1α是SRSF10的一个关键靶点，它通过禁食来调节葡萄糖的产生。SRSF10抑制了PGC1α外显子7a的包含，促进了功能蛋白的产生。这些结果强调了SRSF10和体内受调控的选择性剪接的生物学意义。
Alternative splicing is a major mechanism of controlling gene expression and protein diversity in higher eukaryotes. We report that the splicing factor SRSF10 functions during striated muscle development, myoblast differentiation, and glucose production both in cells and in mice. A combination of RNA-sequencing and molecular analysis allowed us to identify muscle-specific splicing events controlled by SRSF10 that are critically involved in striated muscle development. Inclusion of alternative exons 16 and 17 of Lrrfip1 is a muscle-specific event that is activated by SRSF10 and essential for myoblast differentiation. On the other hand, in mouse primary hepatocytes, PGC1 alpha is a key target of SRSF10 that regulates glucose production by fasting. SRSF10 represses inclusion of PGC1 alpha exon 7a and facilitates the production of functional protein. The results highlight the biological significance of SRSF10 and regulated alternative splicing in vivo.