识别调节表达的MYC内2区域
Van S Tompkins1, Zheng Xue1, Jake M Peterson1
1Roy J. Carver Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, Iowa, United States of America.
PloS one
|January 18, 2024
概括
异质核核核糖核蛋白C (HNRNPC) 结合MYC内核2的多U区域,确保精确的拼接和翻译. 破坏这些部位会损害MYC的产生,突出显示HNRNPC在基因表达中的关键作用.
科学领域:
- 分子生物学分子生物学
- 基因规则 基因规则
- 在RNA分离过程中.
背景情况:
- MYC转录因子对于分化和增殖等细胞过程至关重要.
- 控制MYC前mRNA拼接的精确机制尚不清楚.
- 异质核核核糖核蛋白C (HNRNPC) 是一种关键的RNA结合蛋白.
研究的目的:
- 调查HNRNPC和MYC内部2之间的相互作用.
- 阐明HNRNPC在MYC前mRNA拼接和翻译中的作用.
- 为了确定MYC内部的监管元素2.
主要方法:
- 利用已公布的eCLIP数据来确认HNRNPC的结合点.
- 在MYC内2中对多U区域进行突变分析.
- 分析了对HNRNPC结合,拼接保真性和翻译效率的影响.
- 检查了跨物种识别的结合区域的序列保护.
主要成果:
- 已确认的HNRNPC与MYC内部2的特定多 (U) 区域结合.
- 证明,破坏所有三个多U) 位点显著降低了HNRNPC的结合,并损害了拼接和翻译的准确性.
- 发现这些poly(U) 序列在多个物种中都保持着.
- 确定了一个HNRNPC绑定站点上游的新型监管元素,在删除时可以增强MYC翻译.
结论:
- 在保持MYC前mRNA拼接和翻译忠实性方面,HNRNPC通过其与内基多元U) 区域的相互作用,发挥了关键的补偿作用.
- 已识别的保存序列和调控元素为理解和潜在地操纵MYC基因表达提供了新的目标.
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