内部保留通过抑制mRNA向细胞质出口来降低METTL3表达
Sangsoo Lee1, Haesoo Jung1, Sunkyung Choi1
1Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 34134, Korea.
BMB reports
|June 26, 2023
概括
替代拼接调节了甲基转移酶类3 (METTL3) 的表达. 内部保留会产生新的3'-UTR,抑制mRNA输出并抑制METTL3蛋白水平.
科学领域:
- 分子生物学分子生物学
- 基因规则 基因规则
- 在RNA生物学,RNA生物学.
背景情况:
- 甲基转移酶样3 (METTL3) 对于m6A修饰至关重要,影响基因表达.
- 替代拼接 (AS) 在调节METTL3表达中的作用尚不清楚.
研究的目的:
- 研究替代拼接调节METTL3基因表达的机制.
- 识别和描述由AS产生的新型METTL3异型.
主要方法:
- 对人类组织中METTL3替代拼接模式的分析.
- 使用分子技术确认引发METTL3-IR异型的内质保留 (IR).
- 免疫光显微镜测定METTL3和METTL3-IR.的细胞内定位.
- 评估mRNA和蛋白质表达水平.
主要成果:
- 鉴定了一种新型的METTL3异型 (METTL3-IR),该异型是因8号和9号内子保留而产生的.
- 证实了METTL3和METTL3-IR蛋白质的明显细胞内定位.
- 观察到METTL3-IR mRNA和蛋白质表达水平之间的差异.
- 证明IR产生的3'-UTR抑制了METTL3-IRmRNA的细胞质出口,抑制了蛋白质合成.
结论:
- 这项研究提供了通过替代拼接调节METTL3基因表达的第一个证据.
- 通过内部保留介导的3'-UTR生成通过抑制mRNA出口来抑制METTL3蛋白表达.
- 这种机制突出了METTL3.3的新型转录后基因调节层.
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