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<p>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, m<sup>1</sup>A exhibited significant differences across multiple cell types and between cancerous and non-cancerous cells. Knocking down mRNA m<sup>1</sup>A writer or eraser protein resulted in altered cell viability, cell cycle and apoptosis in HeLa cells, suggesting a role of mRNA m<sup>1</sup>A in cancer. Transcriptomic and proteomic analyses further revealed the molecular mechanisms underlying the phenotypic variation.</p>

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Quantifying the mRNA epitranscriptome reveals epitranscriptome signatures and roles in cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月28日

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  • Ying Feng,
  • Xiaoli He,
  • Mingxin Guo,
  • Ying Tang,
  • Guantong Qi,
  • Qian Huang,
  • Wenran Ma,
  • Hong Chen,
  • Yifan Qin,
  • Ruiqi Li,
  • Jin Wang,
  • Yu Liu

摘要

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.