Alternative splicing transitions associate with emerging atrophy phenotype during denervation-induced skeletal muscle atrophy
Alternative splicing transitions associate with emerging atrophy phenotype during denervation-induced skeletal muscle atrophy
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DOI：
10.1002/jcp.30167
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发表时间：
2020-12-15
影响因子：
5.6
通讯作者：
Sun, Junjie
中科院分区：
文献类型：
--
作者：
Qiu, Jiaying;Wu, Liucheng;Sun, Junjie
选择性剪接（AS）提出了一个关键的转录后调控机制，与许多生理过程相关。然而，人们对其在骨骼肌萎缩中的作用知之甚少。在这项研究中，我们使用大鼠去神经支配骨骼肌萎缩模型，并进行rna测序，分析胫骨前肌在去神经支配后多个时间点的转录组谱。我们发现AS是一种涉及肌肉萎缩的新机制，它在转录水平上是独立的变化。生物信息学分析进一步揭示了AS的转变与萎缩表型的出现有关。此外，我们发现在去神经支配后3天，多个高度保守的obn外显子的包含明显增加。此外，我们证实了这个新的转录物抑制C2C12细胞增殖并加剧肌管萎缩。最后，我们的研究发现，当出现萎缩表型时，大量rna结合蛋白上调。我们的数据强调了AS在这个过程中的重要性。
Alternative splicing (AS) presents a key posttranscriptional regulatory mechanism associated with numerous physiological processes. However, little is known about its role in skeletal muscle atrophy. In this study, we used a rat model of denervated skeletal muscle atrophy and performed RNA-sequencing to analyze transcriptome profiling of tibialis anterior muscle at multiple time points following denervation. We found that AS is a novel mechanism involving muscle atrophy, which is independent changes at the transcript level. Bioinformatics analysis further revealed that AS transitions are associated with the appearance of the atrophic phenotype. Moreover, we found that the inclusion of multiple highly conserved exons of Obscn markedly increased at 3 days after denervation. In addition, we confirmed that this newly transcript inhibited C2C12 cell proliferation and exacerbated myotube atrophy. Finally, our study revealed that a large number of RNA-binding proteins were upregulated when the atrophy phenotype appeared. Our data emphasize the importance of AS in this process.