mRNA甲基化通过向IL-7/STAT5/SOCS通路来控制T细胞平衡
Hua-Bing Li1, Jiyu Tong1,2, Shu Zhu1
1Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Nature
|August 10, 2017
概括
这项研究揭示了N6-甲基氨酸 (m6A) RNA修饰在T细胞生物学中的in vivo作用. 在T细胞中删除m6A编辑器METTL3会破坏免疫细胞平衡和分化.
科学领域:
- 免疫学
- 表观遗传学
- 分子生物学
背景情况:
- N6-甲基氨酸 (m6A) 是最常见的mRNA修饰,在体外影响mRNA代谢.
- 在成年哺乳动物细胞,特别是T细胞中,其体内生理功能在很大程度上是未知的.
研究的目的:
- 研究m6A"写字"蛋白METTL3在哺乳动物T细胞功能的体内作用.
- 阐明m6A影响T细胞稳态和分化的机制.
主要方法:
- 在小鼠T细胞中删除METTL3基因.
- 将Mettl3缺乏的T细胞转移到淋巴发病的小鼠中.
- 对T细胞平衡,分化,基因表达和mRNA衰变率的分析.
主要成果:
- 在转移模型中,缺乏Mettl3的天真T细胞未能扩大和分化,从而预防大肠炎.
- SOCS家族基因mRNAs的m6A修饰导致Mettl3缺乏T细胞的衰变速度减慢和表达增加.
- 增加的SOCS活性抑制了IL-7介导的STAT5激活,损害了T细胞的增殖和分化.
结论:
- 通过METTL3进行的m6A修饰对于维持体内T细胞平衡和分化至关重要.
- 在对IL-7信号的反应中,m6A调节SOCS基因的诱导性mRNA降解.
- 这项研究揭示了m6A在T细胞生物学和发病过程中的新机制.
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