Nuclear RNAi maintains heritable gene silencing in Caenorhabditis elegans
Nuclear RNAi maintains heritable gene silencing in Caenorhabditis elegans
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DOI：
10.1073/pnas.1113310108
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发表时间：
2011-12-06
影响因子：
11.1
通讯作者：
Kennedy, Scott
中科院分区：
文献类型：
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作者：
Burton, Nick O.;Burkhart, Kirk B.;Kennedy, Scott
RNA干扰(RNAi)在秀丽线虫中是可遗传的；暴露于dsRNA的线虫后代继承了前一代RNAi靶向的基因沉默的能力。在这里，我们研究了线虫中RNAi遗传的机制。我们发现，动物暴露在dsRNA中会导致siRNAs的可遗传表达和子代中组蛋白3赖氨酸9甲基化(H3K9me)标记的可遗传沉积。在H3K9me标记出现之前就可以检测到siRNA，这表明染色质标记不是直接遗传的，而是在后代遗传中重建的。有趣的是，与直接接触dsRNA的动物相比，H3K9me标记在遗传后代中出现得更明显，这表明沉默信号的胚系传递可能会提高siRNA导向的H3K9me的效率。最后，我们发现在线虫中，核RNAi(Nrde)途径维持着可遗传的RNAi沉默。ArgAerte(AGO)NRDE-3与可遗传的siRNAs结合，并与核RNAi因子NRDE-1、NRDE-2和NRDE-4共同作用，促进遗传后代的siRNA表达。这些结果表明在线虫中siRNA的表达是可遗传的，并定义了一条RNAi途径，该途径促进了暴露于dsRNA的动物后代中RNAi沉默和siRNA表达的维持。
RNA interference (RNAi) is heritable in Caenorhabditis elegans; the progeny of C. elegans exposed to dsRNA inherit the ability to silence genes that were targeted by RNAi in the previous generation. Here we investigate the mechanism of RNAi inheritance in C. elegans. We show that exposure of animals to dsRNA results in the heritable expression of siRNAs and the heritable deposition of histone 3 lysine 9 methylation (H3K9me) marks in progeny. siRNAs are detectable before the appearance of H3K9me marks, suggesting that chromatin marks are not directly inherited but, rather, reestablished in inheriting progeny. Interestingly, H3K9me marks appear more prominently in inheriting progeny than in animals directly exposed to dsRNA, suggesting that germ-line transmission of silencing signals may enhance the efficiency of siRNA-directed H3K9me. Finally, we show that the nuclear RNAi (Nrde) pathway maintains heritable RNAi silencing in C. elegans. The Argonaute (Ago) NRDE-3 associates with heritable siRNAs and, acting in conjunction with the nuclear RNAi factors NRDE-1, NRDE-2, and NRDE-4, promotes siRNA expression in inheriting progeny. These results demonstrate that siRNA expression is heritable in C. elegans and define an RNAi pathway that promotes the maintenance of RNAi silencing and siRNA expression in the progeny of animals exposed to dsRNA.