Human DCP1 is crucial for mRNA decapping and possesses paralog-specific gene regulating functions
Ting-Wen Chen,
Hsiao-Wei Liao,
Michelle Noble,
Jing-Yi Siao,
Yu-Hsuan Cheng,
Wei-Chung Chiang,
Yi-Tzu Lo,
Chung-Te Chang
Affiliations
Ting-Wen Chen
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; Center for Intelligent Drug Systems and Smart Bio-devices (IDS2 B), National Yang Ming Chiao Tung University, Hsinchu, Taiwan
Hsiao-Wei Liao
Department of Pharmacy, National Yang Ming Chiao Tung University, Taipei City, Taiwan
Michelle Noble
Department of Biochemistry, Max Planck Institute for Developmental Biology, Tübingen, Germany
Jing-Yi Siao
Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei, Taiwan
Yu-Hsuan Cheng
Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei, Taiwan
Wei-Chung Chiang
Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei, Taiwan
Yi-Tzu Lo
Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
Department of Biochemistry, Max Planck Institute for Developmental Biology, Tübingen, Germany; Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei, Taiwan
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.
