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  3. Quantifying the mRNA epitranscriptome reveals epitranscriptome signatures and roles in cancer

Quantifying the mRNA epitranscriptome reveals epitranscriptome signatures and roles in cancer

  • Cell Mol Life Sci. 2025 Jul 28;82(1):290. doi: 10.1007/s00018-025-05805-7.
Ying Feng 1,  Xiaoli He 1,  Mingxin Guo 1,  Ying Tang 1,  Guantong Qi 1,  Qian Huang 1,  Wenran Ma 1,  Hong Chen 1,  Yifan Qin 1,  Ruiqi Li 1,  Jin Wang 2,  Yu Liu 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institute of Biomedical Sciences, School of Life Sciences, Inner Mongolia University, Hohhot, People's Republic of China.
  • 2 State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institute of Biomedical Sciences, School of Life Sciences, Inner Mongolia University, Hohhot, People's Republic of China. jinwang@imu.edu.cn.
  • 3 State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institute of Biomedical Sciences, School of Life Sciences, Inner Mongolia University, Hohhot, People's Republic of China. yuliu@imu.edu.cn.
PMID: 40719884 DOI: 10.1007/s00018-025-05805-7
Abstract

Post-transcriptional modifications on mRNA are crucial for mRNA fate and function. The current lack of a comprehensive method for high-coverage and sensitive quantitative analysis of mRNA modifications significantly limits the discovery of new mRNA modifications and understanding mRNA modifications' occurrence, dynamics and function. Here, a highly sensitive, high-throughput and robust LC-MS/MS-based technique, mRQuant, was developed to simultaneously detect and quantify 84 modified ribonucleosides in cellular mRNA. Using mRQuant, we quantified 32-34 modified ribonucleosides across several human Cancer and non-cancer cell lines and uncovered cancer- and Cancer type-specific signatures. Analyses of cisplatin- and paclitaxel-treated HeLa cells and drug-resistant variants revealed several drug resistance-associated modifications. Among them, m1A exhibited significant differences across multiple cell types and between cancerous and non-cancerous cells. Knocking down mRNA m1A writer or eraser protein resulted in altered cell viability, cell cycle and Apoptosis in HeLa cells, suggesting a role of mRNA m1A in Cancer. Transcriptomic and proteomic analyses further revealed the molecular mechanisms underlying the phenotypic variation.

Keywords

Cancer; Drug resistance; RNA modification; m1A; mRQuant.

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