一个双胞胎UGUA动机通过CFIm和mTORC1信号通路指导基因异型之间的平衡
R Samuel Herron1, Alexander K Kunisky1, Jessica R Madden1
1Department of Pathology, University of Pittsburgh, Pittsburgh, United States.
eLife
|September 4, 2023
概括
mTORC1通路通过控制替代多基化 (APA) 来调节基因表达,特别是平衡两个Trim9异型. 这种机制涉及CPSF6和保存的双胞胎UGUA动机,可能与癌症和神经系统疾病有关.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 细胞信号传递 细胞信号传递
背景情况:
- 替代多氨基化 (APA) 是产生mRNA多样性和调节基因表达的一个关键机制.
- mTORC1信号通路在细胞生长,新陈代谢和增殖中发挥着至关重要的作用.
- mTORC1通路的失调与各种疾病有关,包括癌症和神经系统疾病.
研究的目的:
- 为了研究mTORC1信号通路在调节Trim9异型的替代多基化 (APA) 中的作用.
- 确定涉及mTORC1-介导的APA调节中的分子机制和序列元素.
- 探索这种调节机制在人类疾病中的更广泛影响.
主要方法:
- 在人类和小鼠细胞中对Trim9异型表达的分析.
- 在APA.中调查CFIm组件 (CPSF6和NUDT21) 的功能.
- 在多基化位点中识别和表征保存序列图案 (双UGUA).
- 在异质基因环境中对双胞胎UGUA基因的功能验证.
主要成果:
- mTORC1通路通过APA平衡了两个Trim9异型 (Trim9-S和Trim9-L) 的表达.
- CFIm组件CPSF6和NUDT21促进了短Trim9异型 (Trim9-S) 的表达.
- 在Trim9-S多基化位点中保存的双UGUA基因对CPSF6-介导调节至关重要,这种机制也在其他基因如BMPR1B,MOB4和BRD4-L中观察到.
结论:
- mTORC1通路利用APA通过一种涉及CPSF6和双胞胎UGUA动机的保守机制来调节基因异型表达.
- 这种调节途径提供了关于基因同型失衡如何可能导致与mTORC1失调相关的疾病的见解.
- 这些发现突出了关键信号通路与转录后基因调节之间的新联系,具有潜在的治疗意义.
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