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
  • 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. [email protected].
  • 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. [email protected].
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.
Products