SCAF4和SCAF8,mRNA抗终结蛋白
Lea H Gregersen1, Richard Mitter2, Alejandro P Ugalde3
1Mechanisms of Transcription Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Cell
|May 21, 2019
概括
SCAF4和SCAF8蛋白通过抑制替代多基化位,防止mRNA过早终止. 它们的联合缺失导致截断的mRNA,非功能性蛋白质和细胞死亡,突出显示它们在基因表达调节中的重要作用.
科学领域:
- 分子生物学
- 基因表达的调节
- 进行RNA处理
背景情况:
- 精确的信使RNA (mRNA) 终结对于适当的基因表达至关重要.
- 替代多化 (polyA) 位点可能导致过早终止和非功能转录.
研究的目的:
- 调查SCAF4和SCAF8蛋白在mRNA终结和多化位点选择中的作用.
- 阐明SCAF4和SCAF8调节转录终止的机制.
主要方法:
- 对SCAF4和SCAF8蛋白与酸化RNAPIIC终端重复域 (CTD) 的结合进行分析.
- 在人类细胞中研究多A位点选择和mRNA终结,同时进行SCAF4和SCAF8淘汰.
- 在转录延长和终止中SCAF4和SCAF8独立功能的表征.
主要成果:
- SCAF4 和 SCAF8 作为抗终止剂,抑制早期,替代的多A位点的使用.
- 这些蛋白质与多化RNAPIICTD (Ser2和Ser5) 结合在不同的多A位点.
- 同时淘汰SCAF4和SCAF8会导致多A选择的改变,早期终止,切断mRNA,并且是细胞致命的.
- SCAF8作为RNAPII延长因子,而SCAF4在SCAF8存在时对于正规终结至关重要.
结论:
- SCAF4 和 SCAF8 冗余地抑制早期mRNA终结,但具有不同的非必需功能.
- SCAF4和SCAF8一起协调RNAPII延长和终结之间的过渡.
- 这些蛋白质确保了人体细胞中正确的多A位点选择和转录终止,保持了基因表达的忠实性.
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