解读自然酵母转录领导者中cis作用序列的景观
Christina Akirtava1,2, Gemma E May1, C Joel McManus1,3
1Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, United States.
Nucleic acids research
|March 12, 2025
概括
酵母5'转录领导者 (TLs) 显著调节基因表达. 虽然Kozak语境和上游AUG解释了一些变异,但其他cis作用特征对于精确控制翻译和mRNA稳定性至关重要.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生物化学
背景情况:
- 蛋白质合成在翻译启动时受到严格调节.
- 细胞5'转录领导者 (TLs) 具有影响翻译和mRNA稳定性的cis作用元素.
- 这些特征在自然TL的定量影响仍然不太清楚.
研究的目的:
- 系统量化自然酵母TLs中的序列特征对体内基因表达的影响.
- 为了比较不同cis作用元素对整体基因表达变异的相对贡献.
- 研究替代转录起点在基因表达调节中的作用.
主要方法:
- 使用大规模并行报告测试 (MPRA) 分析了 11,027 个天然酵母TL.
- 量化RNA水平,核糖体负载和蛋白质输出 in vivo.
- 系统地评估了序列特征对基因表达的影响.
主要成果:
- 酵母TL集体影响基因表达在两个数量级.
- 一个漏洞扫描模型 (Kozak语境和上游AUG) 占表达差异的50%.
- 结合额外的cis作用特征解释了大约80%的基因表达变异.
- 替代转录起点对基因表达的量化影响.
结论:
- 确定和量化了调节酵母TLs基因表达的关键cis作用序列特征.
- 证明了传统的漏洞扫描模型之外的多个特征对于全面的基因表达控制至关重要.
- 提供了对TLs在调节翻译和mRNA稳定性的体内作用的定量见解.
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