Paf1复合体抑制了小RNA介导的表观遗传基因沉默
Katarzyna Maria Kowalik1,2, Yukiko Shimada1,2, Valentin Flury1,2
1Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Nature
|March 26, 2015
概括
现在RNA干扰 (RNAi) 可以启动稳定的基因沉默和表观遗传记忆. 通常情况下,RNA聚合酶相关因子1复合体 (Paf1C) 会阻止这种发生,但在Paf1C突变体中,小干扰RNAs (siRNAs) 会触发持久的异染色蛋白形成.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 基因规则 基因规则
背景情况:
- RNA干扰 (RNAi) 通过小干扰RNA (siRNAs) 沉默基因表达.
- 内源性小RNA对染色质调节至关重要,但使用siRNAs在转基因中诱导染色质变化是具有挑战性的.
- RNA聚合酶相关因子1复合体 (Paf1C) 是转录的保守调节者.
研究的目的:
- 为了研究Paf1C在RNAi导向的异染色蛋白形成中的作用.
- 为了揭示控制表观遗传基因沉默的机制,由转基因作用siRNAs启动.
- 了解表观遗传记忆是如何建立和维护的.
主要方法:
- 使用裂变酵母作为模型系统.
- 引入了合成毛RNA来触发RNAi.
- 生成并分析了Paf1C突变体.
- 评估 heterochromatin 的形成和基因沉默.
- 研究了转录终止和新生的转录释放.
主要成果:
- Paf1C可以负面控制RNAi导向的异染色蛋白形成.
- Paf1C突变使合成siRNAs能够诱导稳定,转基因作用的异染色蛋白和基因沉默.
- 这种沉默状态通过二级siRNAs传递到代后代.
- Paf1C促进转录终止和新生的转录释放,防止siRNA向.
- 损坏的转录终止和新生的转录释放对于稳定的表观遗传沉默至关重要.
结论:
- Paf1C作为siRNA介导的表观遗传基因沉默的障碍.
- 破坏Paf1C功能可以通过RNAi建立稳定的异染色素和表观遗传记忆.
- 这项研究揭示了小型RNA引导表观基因组调节的新机制,并突出了Paf1C在表观基因遗传中的作用.
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