Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China.
State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, China.
Int J Mol Sci. 2024 Sep 27;25(19):10396. doi: 10.3390/ijms251910396.
As a reader of tri-methylated lysine 36 on histone H3 (H3K36me3), Npac has been shown to have a significant role in gene transcription elongation. However, its potential implication in RNA splicing remains unknown. Here, we characterized the phenotypes of knockout in mES cells. We discovered that loss of Npac disrupts pluripotency and identity in mESCs. We also found that Npac is associated with many cellular activities, including cell proliferation, differentiation, and transcription regulation. Notably, we uncovered that Npac is associated with RNA splicing machinery. Furthermore, we found that Npac regulates alternative splicing through its interaction with the splicing factors, including Srsf1. Our research thus highlights the important role of Npac in maintaining ESC identity through the regulation of pre-mRNA splicing.
作为组蛋白 H3 上三甲基化赖氨酸 36(H3K36me3)的读取蛋白,NPAC 在基因转录延伸中起着重要作用。然而,其在 RNA 剪接中的潜在作用尚不清楚。在这里,我们对 mES 细胞中的 NPAC 敲除表型进行了特征描述。我们发现 NPAC 的缺失破坏了 mESCs 的多能性和身份。我们还发现 NPAC 与许多细胞活动有关,包括细胞增殖、分化和转录调控。值得注意的是,我们发现 NPAC 与 RNA 剪接机制有关。此外,我们发现 NPAC 通过与剪接因子(包括 Srsf1)相互作用来调节可变剪接。我们的研究因此强调了 NPAC 通过调节前体 mRNA 剪接在维持 ESC 特性方面的重要作用。