RBM20-Mediated Pre-mRNA Splicing Has Muscle-Specificity and Differential Hormonal Responses between Muscles and in Muscle Cell Cultures.

RBM20-Mediated Pre-mRNA Splicing Has Muscle-Specificity and Differential Hormonal Responses between Muscles and in Muscle Cell Cultures.
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RBM20介导的前mRNA剪接具有肌肉特异性和肌肉之间和肌肉细胞培养物中的差异激素反应。

DOI:
10.3390/ijms22062928
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发表时间:
2021-03-13
影响因子:
5.6
通讯作者:
Guo W
Guo W
中科院分区:
生物学2区
文献类型:
--
作者:
Maimaiti R;Zhu C;Zhang Y;Ding Q;Guo W

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前体mRNA剪接在肌肉功能和疾病中起着重要作用。RNA结合基序20(RBM20)是一种剪接因子,主要在肌肉组织中表达,并主要调节Ttn的前mRNA剪接,编码一种负责肌肉功能和疾病的巨大肌肉蛋白肌联蛋白。RBM20介导的Ttn剪接主要在心肌中研究,但在骨骼肌中没有研究。在这项研究中,我们研究了Rbm20基因敲除大鼠不同肌肉类型的剪接特异性,以及激素对Rbm20介导的细胞内和体内剪接的影响。结果显示,RBM20在肌肉中差异表达,并且RBM20介导的剪接是肌肉类型特异性的。在RBM20的存在下,Ttn剪接以肌肉类型依赖的方式响应激素,而在RBM20的不存在下,Ttn剪接不受激素的影响。在分化和未分化的C2C12细胞中,RBM20介导的剪接响应激素的作用主要是通过基因组信号通路。从这项研究中获得的知识可能有助于进一步了解不同肌肉类型中响应激素刺激的肌肉特异性基因剪接。
Pre-mRNA splicing plays an important role in muscle function and diseases. The RNA binding motif 20 (RBM20) is a splicing factor that is predominantly expressed in muscle tissues and primarily regulates pre-mRNA splicing of Ttn, encoding a giant muscle protein titin that is responsible for muscle function and diseases. RBM20-mediated Ttn splicing has been mostly studied in heart muscle, but not in skeletal muscle. In this study, we investigated splicing specificity in different muscle types in Rbm20 knockout rats and hormonal effects on RBM20-mediated splicing both in cellulo and in vivo studies. The results revealed that RBM20 is differentially expressed across muscles and RBM20-mediated splicing is muscle-type specific. In the presence of RBM20, Ttn splicing responds to hormones in a muscle-type dependent manner, while in the absence of RBM20, Ttn splicing is not affected by hormones. In differentiated and undifferentiated C2C12 cells, RBM20-mediated splicing in response to hormonal effects is mainly through genomic signaling pathway. The knowledge gained from this study may help further understand muscle-specific gene splicing in response to hormone stimuli in different muscle types.
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