解读天然酵母的cis监管格局 转录领导者
Christina Akirtava1,2, Gemma May1, C Joel McManus1,3
1Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, 15213, USA.
bioRxiv : the preprint server for biology
|July 15, 2024
概括
研究酵母5'转录领导者 (TLs) 揭示了它们对基因表达的重大影响. 关键序列特征和替代起点集体解释了翻译和mRNA稳定性的大部分变化.
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:
- 调节蛋白质合成是至关重要的,特别是在翻译启动时.
- 细胞5'转录领导者 (TLs) 具有影响翻译和mRNA稳定性的cis-regulatory元素.
- 这些特征在自然TL的确切影响仍然不完全理解.
研究的目的:
- 系统量化自然酵母TL中的序列特征对基因表达的影响.
- 为了比较TL特征的体内效应与对核糖体招募的体内发现.
- 评估替代转录起点使用对基因表达变异性的贡献.
主要方法:
- 采用了大规模并行报告测试 (MPRA) 来分析11,027个天然酵母TLs.
- 量化RNA水平,核糖体负载和蛋白质输出 in vivo.
- 系统地评估了各种序列特征对基因表达的相对贡献.
主要成果:
- 酵母TLs在基因表达影响方面显示出两级大小的范围.
- 一个包含Kozak语境和上游AUGs (uAUGs) 的漏洞扫描模型解释了50%的表达差异.
- 包括额外的特征改善了基因表达变异的解释大约70%.
结论:
- 确定和量化了调节基因表达的关键cis作用序列特征 in vivo.
- 证明TL序列特征和替代转录起点是基因表达的主要决定因素.
- 提供了新的定量洞察力,了解TL在酵母中的cis作用序列的调节作用.
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