Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
Elife. 2024 Nov 1;13:RP94811. doi: 10.7554/eLife.94811.
The mRNA 5'-cap structure removal by the decapping enzyme DCP2 is a critical step in gene regulation. While DCP2 is the catalytic subunit in the decapping complex, its activity is strongly enhanced by multiple factors, particularly DCP1, which is the major activator in yeast. However, the precise role of DCP1 in metazoans has yet to be fully elucidated. Moreover, in humans, the specific biological functions of the two DCP1 paralogs, DCP1a and DCP1b, remain largely unknown. To investigate the role of human DCP1, we generated cell lines that were deficient in DCP1a, DCP1b, or both to evaluate the importance of DCP1 in the decapping machinery. Our results highlight the importance of human DCP1 in decapping process and show that the EVH1 domain of DCP1 enhances the mRNA-binding affinity of DCP2. Transcriptome and metabolome analyses outline the distinct functions of DCP1a and DCP1b in human cells, regulating specific endogenous mRNA targets and biological processes. Overall, our findings provide insights into the molecular mechanism of human DCP1 in mRNA decapping and shed light on the distinct functions of its paralogs.
mRNA 5'-帽结构的去除由脱帽酶 DCP2 完成，这是基因调控的关键步骤。虽然 DCP2 是脱帽复合物的催化亚基，但它的活性受到多种因素的强烈增强，特别是 DCP1，它是酵母中的主要激活剂。然而，DCP1 在后生动物中的精确作用尚未完全阐明。此外，在人类中，两个 DCP1 同源物（DCP1a 和 DCP1b）的特定生物学功能仍知之甚少。为了研究人类 DCP1 的作用，我们生成了缺乏 DCP1a、DCP1b 或两者的细胞系，以评估 DCP1 在脱帽机制中的重要性。我们的结果强调了人类 DCP1 在脱帽过程中的重要性，并表明 DCP1 的 EVH1 结构域增强了 DCP2 与 mRNA 的结合亲和力。转录组和代谢组分析概述了 DCP1a 和 DCP1b 在人类细胞中的不同功能，调节特定的内源性 mRNA 靶标和生物学过程。总的来说，我们的研究结果为人类 DCP1 在 mRNA 脱帽中的分子机制提供了新的见解，并阐明了其同源物的不同功能。
