PRPS2通过依赖酶和独立机制刺激SAM合成来增强RNAm6A甲基化
Lin Zhang1, Xian Zhao2, Jingyan Hu1
1Department of Pharmacology and Chemical Biology, State Key Laboratory of Systems Medicine for Cancer, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China.
Nature communications
|April 28, 2025
概括
癌细胞使用PRPS2来促进RNA甲基化S-adenosylmethionine (SAM) 生产,从而推动肺瘤的生长. 这一发现揭示了核酸合成与癌症表观遗传学之间的新联系.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 癌细胞重编程新陈代谢以支持诸如RNA甲基化之类的表观遗传变化.
- S-adenosylmethionine (SAM) 对于RNA甲基化至关重要,但其在癌症中的产生尚未完全理解.
研究的目的:
- 阐明癌细胞产生SAM以维持RNA甲基化的机制.
- 研究PRPS2在调节RNA甲基化和促进肺癌发生中的作用.
主要方法:
- 研究了PRPS2在调节RNA甲基化中的功能.
- 分析了PRPS2与MAT2A和WTAP/METTL3/METTL14复合物的相互作用.
- 研究了PRPS2对ATP产生和SAM合成的影响.
主要成果:
- 与PRPS1不同,PRPS2绕过反抑制以过度产生ATP,与PRPS1不同.
- PRPS2稳定了MAT2A,增强了RNAm6A甲基化的SAM合成.
- 在PRPS2-MAT2A-WTAP/METTL3/METTL14轴促进肺瘤发生.
结论:
- 在癌症进展中,PRPS2将核酸生物合成与RNA表观遗传联系起来.
- PRPS2既具有依赖酶的功能,也具有独立的致癌功能.
- 准PRPS2通路为癌症提供了潜在的治疗策略.
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