Wdr4通过let-7调节核糖体生物发生和肠道平衡
Kreeti Kajal1,2,3, Elham Rastegari3,4, Wen-Der Wang5
1Molecular and Biological Agricultural Sciences Program, Taiwan International Graduate Program, National Chung Hsing University and Academia Sinica, Taipei, 11529, Taiwan.
WD重复蛋白Wdr4通过控制let-7 miRNA的修饰来调节肠干细胞的恒常性. 这一过程对于防止过度增殖和保持Drosophila中肠组织完整性至关重要.
科学领域:
- 分子生物学分子生物学
- 发展生物学 发展生物学
- 遗传学 是一个遗传学.
背景情况:
- 核糖体生物发生的调节对于干细胞功能和组织恒温至关重要.
- 成人肠干细胞 (ISC) 上游控制机制尚未完全理解.
研究的目的:
- 为了识别Drosophila中肠中的ISC稳态的关键调节者.
- 阐明WD重复蛋白Wdr4在ISC调节中的作用.
主要方法:
- 研究了 Wdr4 在 Drosophila 中肠 ISC 的功能.
- 分析了Wdr4,Mettl1和let-7miRNA之间的相互作用.
- 评估了Wdr4/Mettl1耗尽对信号通路 (TOR-JNK-dMyc) 和核糖体生物发生的影响.
- 利用基因操纵 (耗尽,过度表达) 和人类正义学家的救援实验.
主要成果:
- Wdr4,与甲基转移酶Mettl1一起,催化了let-7miRNA的m7G修饰.
- 耗尽Wdr4或Mettl1会破坏let-7的修改,降低let-7水平,并激活TOR-JNK-dMyc信号传输.
- 这导致核糖体生物生成的增加,ISC的过度扩散,差异化错误,以及肠道发育不良.
- 人类的WDR4和METTL1恢复了ISC的平衡,这表明功能得到保护.
结论:
- 保存的Wdr4/Mettl1-let-7-TOR-JNK轴将miRNA修饰与翻译控制和组织完整性联系起来.
- miRNA m7G甲基化是核糖体生物发生和肠道平衡的一个新型调节剂.
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