Faculty of Biology and Biotechnology, National Research University Higher School of Economics, Moscow, Russia.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Dokl Biochem Biophys. 2023 Jun;510(1):99-103. doi: 10.1134/S1607672923700199. Epub 2023 Aug 15.
The expression of RNA-binding proteins and their interaction with the spliced pre-mRNA are the key factors in determining the final isoform profile. Transmembrane protein CD44 is involved in differentiation, invasion, motility, growth and survival of tumor cells, and is also a commonly accepted marker of cancer stem cells and epithelial-mesenchymal transition. However, the functions of the isoforms of this protein differ significantly. In this paper, we developed a method based on the boosted beta regression algorithm for identification of the significant RNA-binding proteins in the splicing process by modeling the isoform ratio. The application of this method to the analysis of CD44 splicing in colorectal cancer cells revealed 20 significant RNA-binding proteins. Many of them were previously shown as EMT regulators, but for the first time presented as potential CD44 splicing factors.
RNA 结合蛋白的表达及其与剪接前体 mRNA 的相互作用是决定最终异构体谱的关键因素。跨膜蛋白 CD44 参与肿瘤细胞的分化、浸润、迁移、生长和存活，也是公认的癌症干细胞和上皮-间充质转化的标志物。然而，该蛋白的异构体功能差异很大。在本文中，我们开发了一种基于提升贝叶斯回归算法的方法，通过建立异构体比例模型来识别剪接过程中的显著 RNA 结合蛋白。将该方法应用于结直肠癌细胞 CD44 剪接的分析中，揭示了 20 个显著的 RNA 结合蛋白。其中许多蛋白先前被证明是 EMT 调节剂，但首次被认为是潜在的 CD44 剪接因子。
