Animal Science Department, University of Wyoming, Laramie, WY 82071, USA.
Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
Int J Mol Sci. 2021 Mar 13;22(6):2928. doi: 10.3390/ijms22062928.
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.
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，主要调节编码巨大肌肉蛋白肌联蛋白（titin）的 Ttn 前体 mRNA 的剪接，肌联蛋白负责肌肉功能和疾病。RBM20 介导的 Ttn 剪接主要在心肌中进行研究，但在骨骼肌中尚未进行研究。在这项研究中，我们在 Rbm20 敲除大鼠中研究了不同肌肉类型中的剪接特异性以及激素对细胞内和体内 RBM20 介导的剪接的影响。结果表明，RBM20 在不同肌肉中表达不同，RBM20 介导的剪接具有肌肉特异性。在存在 RBM20 的情况下，Ttn 剪接以肌肉类型依赖的方式对激素做出反应，而在不存在 RBM20 的情况下，Ttn 剪接不受激素影响。在分化和未分化的 C2C12 细胞中，RBM20 介导的对激素作用的剪接主要通过基因组信号通路进行。本研究获得的知识可能有助于进一步了解不同肌肉类型中激素刺激下肌肉特异性基因剪接。
