# Quantifying the mRNA epitranscriptome reveals epitranscriptome signatures and roles in cancer

## TL;DR

A new method called mRQuant was developed to study mRNA modifications in cancer cells, revealing specific modification patterns linked to cancer and drug resistance.

## Contribution

mRQuant is a novel LC-MS/MS-based technique enabling high-throughput quantification of 84 mRNA modifications, uncovering cancer-specific signatures and drug resistance associations.

## Key findings

- mRQuant detected 32–34 modified ribonucleosides across human cancer and non-cancer cell lines.
- m1A modification showed significant differences between cancerous and non-cancerous cells and was linked to drug resistance.
- Knocking down m1A writer or eraser proteins altered cell viability, cycle, and apoptosis in HeLa cells.

## 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.

The online version contains supplementary material available at 10.1007/s00018-025-05805-7.