SRSF10通过调控可变剪接在成肌细胞分化和葡萄糖生成中发挥作用。
SRSF10 Plays a Role in Myoblast Differentiation and Glucose Production via Regulation of Alternative Splicing.
作者信息
Wei Ning, Cheng Yuanming, Wang Zhijia, Liu Yuguo, Luo Chunling, Liu Lina, Chen Linlin, Xie Zhiqin, Lu Yun, Feng Ying
机构信息
Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Affiliated Hospital of Qingdao University, Qingdao 266003, China.
出版信息
Cell Rep. 2015 Nov 24;13(8):1647-57. doi: 10.1016/j.celrep.2015.10.038. Epub 2015 Nov 12.
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, PGC1α is a key target of SRSF10 that regulates glucose production by fasting. SRSF10 represses inclusion of PGC1α exon 7a and facilitates the production of functional protein. The results highlight the biological significance of SRSF10 and regulated alternative splicing in vivo.
可变剪接是高等真核生物中控制基因表达和蛋白质多样性的主要机制。我们报告称，剪接因子SRSF10在横纹肌发育、成肌细胞分化以及细胞和小鼠体内的葡萄糖生成过程中发挥作用。RNA测序和分子分析相结合使我们能够鉴定出由SRSF10控制的、对横纹肌发育至关重要的肌肉特异性剪接事件。Lrrfip1基因外显子16和17的选择性包含是一个肌肉特异性事件，由SRSF10激活，对成肌细胞分化至关重要。另一方面，在小鼠原代肝细胞中，PGC1α是SRSF10的关键靶点，通过禁食调节葡萄糖生成。SRSF10抑制PGC1α外显子7a的包含，并促进功能性蛋白质的产生。这些结果突出了SRSF10以及体内受调控的可变剪接的生物学意义。
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