HP1Swi6 Mediates the Recognition and Destruction of Heterochromatic RNA Transcripts
HP1Swi6 Mediates the Recognition and Destruction of Heterochromatic RNA Transcripts
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DOI：
10.1016/j.molcel.2012.05.009
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发表时间：
2012-07-27
期刊：
影响因子：
16
通讯作者：
Buehler, Marc
中科院分区：
文献类型：
--
作者：
Keller, Claudia;Adaixo, Ricardo;Buehler, Marc
HP1蛋白是异染色质的主要组成部分，异染色质通常被认为是一种惰性和转录不活跃的染色质结构。然而，HP1与染色质的结合是高度动态的，异色基因的强大沉默可能涉及RNA加工。在这里，我们通过体内和体外实验的结合证明，裂变酵母HP1（Swi6）蛋白通过RNA的隔离和降解保证了对异色基因的严格抑制。在铰链区带正电残基的刺激下，RNA与甲基化组蛋白H3K9竞争，以结合HP1的色域（Swi6）。因此，HP1（Swi6）与RNA结合与稳定的异染色质结合是不相容的。我们提出了一个模型，其中HP1（Swi6）蛋白的集合作为异染色质特异性检查点，捕获和启动异染色质RNA的RNA降解机制。维持功能性检查点需要在异染色质内持续交换HP1(Swi6)，这解释了HP1蛋白在异染色质上的动态定位。
HP1 proteins are major components of heterochromatin, which is generally perceived to be an inert and transcriptionally inactive chromatin structure. Yet, HP1 binding to chromatin is highly dynamic and robust silencing of heterochromatic genes can involve RNA processing. Here, we demonstrate by a combination of in vivo and in vitro experiments that the fission yeast HP1(Swi6) protein guarantees tight repression of heterochromatic genes through RNA sequestration and degradation. Stimulated by positively charged residues in the hinge region, RNA competes with methylated histone H3K9 for binding to the chromodomain of HP1(Swi6). Hence, HP1(Swi6) binding to RNA is incompatible with stable heterochromatin association. We propose a model in which an ensemble of HP1(Swi6) proteins functions as a heterochromatin-specific checkpoint, capturing and priming heterochromatic RNAs for the RNA degradation machinery. Sustaining a functional checkpoint requires continuous exchange of HP1(Swi6) within heterochromatin, which explains the dynamic localization of HP1 proteins on heterochromatin.