METTL3改变了封闭酶的表达及其对核糖体蛋白的活性
Daniel Del Valle-Morales1, Giulia Romano1, Giovanni Nigita2,3
1Department of Internal Medicine, Division of Pulmonary Diseases and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Scientific reports
|November 12, 2024
概括
N6-甲基氨酸 (m6A) 修饰调节RNA甘转移酶和5'-酸酶 (RNGTT) 的表达. 通过METTL3介导的RNGTTmRNA的m6A甲基化降低了RNGTT蛋白水平,影响了细胞质封闭和mTOR通路信号.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 在RNA生物学,RNA生物学.
背景情况:
- 5'盖对于mRNA功能,成熟和基因表达调节至关重要.
- RNA guanylyltransferase和5'-酸酶 (RNGTT) 催化了5'封闭.
- N6-甲基氨酸 (m6A) 是一种普遍存在的RNA修饰,影响mRNA命运和功能.
研究的目的:
- 研究m6A在RNGTT表达和活动中的调控作用.
- 为了确定m6A修饰是否影响RNGTT蛋白水平和mRNA限制效率.
主要方法:
- 西部涂抹测定RNGTT蛋白质水平.
- 通过RNA免疫沉,然后进行测序 (RIP-Seq) 来识别m6A位点.
- 定量实时PCR (qRT-PCR) 用于测量mRNA水平.
- 途径分析 (例如,mTOR,p70S6K) 以了解下游影响.
主要成果:
- RNGTT mRNA的3'未翻译区域 (3'UTR) 被METTL3.3甲基化.
- 抑制METTL3导致RNGTT蛋白表达的降低.
- 细胞质封闭的抑制失调了基因表达,特别是核糖体蛋白和5'终端寡聚胺 (TOP) mRNAs.
- METTL3的淘汰破坏了mTOR和p70S6K的信号通路,减少了RPS6mRNA的封闭,蛋白质的表达和酸化.
结论:
- RNGTT mRNA的METTL3介导的m6A修饰是一种RNGTT表达的新型调节机制.
- RNGTT的m6A依赖调节会影响细胞质mRNA的封闭,影响特定mRNA子集的翻译.
- 这一发现突显了RNA表观遗传修饰与mTOR等关键细胞信号通路之间的联系.
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