Department of Hematopoiesis, Sanquin Research, Amsterdam, The Netherlands.
Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
PLoS One. 2022 Oct 19;17(10):e0276294. doi: 10.1371/journal.pone.0276294. eCollection 2022.
T cells are key players in our defence against infections and malignancies. When T cells differentiate or become activated, they undergo substantial alterations in gene expression. Even though RNA expression levels are now well documented throughout different stages of T cells, it is not well understood how mRNA expression translates into the protein landscape. By combining paired RNA sequencing and mass spectrometry data of primary human CD8+ T cells, we report that mRNA expression is a poor proxy for the overall protein output, irrespective of the differentiation or activation status. Yet, gene class stratification revealed a function-specific correlation of mRNA with protein expression. This gene class-specific expression pattern associated with differences in gene characteristics such as sequence conservation and untranslated region (UTR) lengths. In addition, the presence of AU-rich elements in the 3'UTR associated with alterations in mRNA and protein abundance T cell activation dependent, gene class-specific manner. In conclusion, our study highlights the role of gene characteristics as a determinant for gene expression in T cells.
T 细胞是我们抵御感染和恶性肿瘤的关键因素。当 T 细胞分化或被激活时，它们的基因表达会发生显著改变。尽管现在已经很好地记录了 T 细胞不同阶段的 RNA 表达水平，但人们并不清楚 mRNA 表达如何转化为蛋白质图谱。通过结合原发性人 CD8+T 细胞的配对 RNA 测序和质谱数据，我们报告说，mRNA 表达不能很好地代表整体蛋白质输出，无论分化或激活状态如何。然而，基因分类分层显示了 mRNA 与蛋白质表达之间的功能特异性相关性。这种基因分类特异性表达模式与基因特征的差异有关，如序列保守性和非翻译区 (UTR) 长度。此外，3'UTR 中富含 AU 的元件与 T 细胞激活依赖性的 mRNA 和蛋白质丰度改变有关，具有基因分类特异性。总之，我们的研究强调了基因特征作为 T 细胞基因表达决定因素的作用。
