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Quantifying the mRNA epitranscriptome reveals epitranscriptome signatures and roles in cancer
Ying Feng1, Xiaoli He1, Mingxin Guo1
1State 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.
Cellular and Molecular Life Sciences : CMLS
|July 28, 2025
Summary
A new method, mRQuant, enables sensitive quantification of 84 mRNA modifications. This technique identified cancer-specific modification signatures and revealed the role of N1-methyladenosine (m¹A) in cancer progression and drug resistance.
Area of Science:
- Molecular Biology
- Biochemistry
- Cancer Research
Background:
- Post-transcriptional modifications on mRNA regulate gene expression and cellular function.
- Existing methods for quantifying mRNA modifications lack sensitivity and comprehensive coverage, hindering discovery and functional studies.
Purpose of the Study:
- To develop a highly sensitive, high-throughput, and robust LC-MS/MS-based technique for simultaneous detection and quantification of multiple modified ribonucleosides in mRNA.
- To apply this method to identify mRNA modification signatures in cancer and understand their role in cancer biology and drug resistance.
Main Methods:
- Development and application of mRQuant, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique.
- Quantification of 84 modified ribonucleosides in cellular mRNA across various human cancer and non-cancer cell lines.
- Analysis of drug-treated cells and drug-resistant variants to identify resistance-associated modifications.
Main Results:
- Quantified 32-34 modified ribonucleosides, revealing cancer- and cancer type-specific signatures.
- Identified several drug resistance-associated modifications, with N1-methyladenosine (m¹A) showing significant differences across cell types and between cancerous and non-cancerous cells.
- Demonstrated that manipulating mRNA m¹A levels affects cell viability, cell cycle, and apoptosis, suggesting a role in cancer.
Conclusions:
- mRQuant is a powerful tool for sensitive and comprehensive analysis of mRNA modifications.
- mRNA modifications, particularly m¹A, play a significant role in cancer development, progression, and drug resistance.
- Further transcriptomic and proteomic analyses elucidated the molecular mechanisms underlying the observed phenotypic variations.
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