SRSF10 Regulates Alternative Splicing and Is Required for Adipocyte Differentiation
SRSF10 Regulates Alternative Splicing and Is Required for Adipocyte Differentiation
复制标题
SRSF10 调节选择性剪接并且是脂肪细胞分化所必需的
DOI：
10.1128/mcb.01674-13
复制
发表时间：
2014-06-01
影响因子：
5.3
通讯作者：
Feng, Ying
中科院分区：
文献类型：
--
作者：
Li, Huang;Cheng, Yuanming;Feng, Ying
在脂肪细胞分化过程中，与脂肪形成过程相关的显著的选择性剪接变化发生。然而，很少有人知道剪接因子在这一过程中发挥的作用。我们观察到，剪接因子SRSF 10缺陷的小鼠表现出严重受损的皮下白色脂肪组织（WAT）的发展，作为脂肪形成分化缺陷的结果。为了鉴定对此负责的剪接事件，使用胚胎成纤维细胞进行转录组测序（RNA-seq）分析。已经鉴定了几种与脂肪形成有关的SRSF 10影响的剪接事件。值得注意的是，进一步研究了脂蛋白1，其被认为是脂肪形成过程中的重要调节剂。虽然脂蛋白1 β主要参与脂肪生成，但其通过外显子7跳跃产生的可变剪接同种型脂蛋白1 α主要是初始脂肪细胞分化所需的。外显子7的跳跃由位于组成型外显子8中的SRSF 10调节的顺式元件控制。该元件的活性取决于SRSF 10的结合，并与脂蛋白1 α mRNA的相对丰度相关。一系列实验表明，SRSF 10控制lipin 1 α的产生，从而促进脂肪细胞分化。事实上，脂蛋白1 α表达可以挽救SRSF 10介导的脂肪形成缺陷。总之，我们的研究结果确定SRSF 10作为脂肪细胞分化的重要调节因子，也提供了新的见解SRSF 10在lipin 1前mRNA剪接剪接控制。
During adipocyte differentiation, significant alternative splicing changes occur in association with the adipogenic process. However, little is known about roles played by splicing factors in this process. We observed that mice deficient for the splicing factor SRSF10 exhibit severely impaired development of subcutaneous white adipose tissue (WAT) as a result of defects in adipogenic differentiation. To identify splicing events responsible for this, transcriptome sequencing (RNA-seq) analysis was performed using embryonic fibroblast cells. Several SRSF10-affected splicing events that are implicated in adipogenesis have been identified. Notably, lipin 1, known as an important regulator during adipogenesis, was further investigated. While lipin 1 beta is mainly involved in lipogenesis, its alternatively spliced isoform lipin 1 alpha, generated through the skipping of exon 7, is primarily required for initial adipocyte differentiation. Skipping of exon 7 is controlled by an SRSF10-regulated cis element located in the constitutive exon 8. The activity of this element depends on the binding of SRSF10 and correlates with the relative abundance of lipin 1 alpha mRNA. A series of experiments demonstrated that SRSF10 controls the production of lipin 1 alpha and thus promotes adipocyte differentiation. Indeed, lipin 1 alpha expression could rescue SRSF10-mediated adipogenic defects. Taken together, our results identify SRSF10 as an essential regulator for adipocyte differentiation and also provide new insights into splicing control by SRSF10 in lipin 1 pre-mRNA splicing.