依赖于RNA的表观遗传沉默指导转录下调,由内在重复扩张引起
Hannes Eimer1, Sridevi Sureshkumar1, Avilash Singh Yadav1
1School of Biological Sciences, Monash University, Clayton Campus, VIC 3800, Australia.
Cell
|July 31, 2018
概括
三重重复扩张触发短干扰RNAs (siRNAs) 和表观遗传变化,导致基因沉默. 这种机制涉及RNA依赖DNA甲基化 (RdDM),解释了这些扩张如何导致疾病表型.
科学领域:
- 遗传学
- 表观遗传学
- 分子生物学
背景情况:
- 内部三重复扩张与弗里德里希等疾病有关.
- 基因表达的下调伴随着这些扩张,但机制仍然不清楚.
研究的目的:
- 研究由内基三重复扩张引起的转录下调的分子机制.
- 阐明表观遗传修饰和小RNA在这个过程中的作用.
主要方法:
- 在Arabidopsis thaliana的IIL1基因中对内部GAA/TTC三重扩张的分析.
- 研究DICER LIKE-3 (DCL3) 和依赖RNA的DNA甲基化 (RdDM) 途径组件的作用.
主要成果:
- 在IIL1中,三重复扩张导致24n siRNA积累和压制性基因素标记.
- 抑制了DCL3或RdDM途径组件的IIL1下调和相关的表型.
- siRNA生物发生和RdDM对于重复扩张诱导的基因沉默至关重要.
结论:
- 三重重复扩张可以诱导局部小干扰RNA (siRNA) 的产生.
- 这种siRNA产生通过依赖RNA的DNA甲基化 (RdDM) 调节转录下调.
- 这些发现揭示了一种新的表观遗传机制,
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