X chromosome inactivation in the absence of Dicer
X chromosome inactivation in the absence of Dicer
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DOI：
10.1073/pnas.0812210106
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发表时间：
2009-01-27
影响因子：
11.1
通讯作者：
Livingston, David M.
中科院分区：
文献类型：
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作者：
Kanellopoulou, Chryssa;Muljo, Stefan A.;Livingston, David M.
Dicer 是 RNA 干扰 (RNAi) 途径的核心，因为它是将双链 RNA (dsRNA) 前体加工成小 RNA 效应分子所必需的。原则上，任何长 dsRNA 都可以作为 Dicer 的底物。 X 无活性特异性转录本 (Xist) 是哺乳动物剂量补偿所需的非翻译 RNA。它包裹并沉默雌性细胞中 2 条 X 染色体中的 1 条，并启动染色质结构的染色体范围变化，其中包括招募 Polycomb 蛋白，但目前尚不清楚 Xist RNA 如何介导这些过程。为了研究 RNAi 途径和 X 失活之间的潜在联系，我们生成并分析了 Dicer 缺陷型胚胎干 (ES) 细胞。在没有 Dicer 的情况下，Xist RNA 的包被、沉默的启动和 Polycomb 蛋白的募集正常发生。 Dicer 消融对剪接的 Xist RNA 的稳态水平影响不大。我们的数据表明，RNAi 机制对于 X 失活的启动并不是必需的。
Dicer is central to the RNA interference (RNAi) pathway, because it is required for processing of double-stranded RNA (dsRNA) precursors into small RNA effector molecules. In principle, any long dsRNA could serve as a substrate for Dicer. The X inactive specific transcript (Xist) is an untranslated RNA that is required for dosage compensation in mammals. It coats and silences 1 of the 2 X chromosomes in female cells and initiates a chromosomewide change in chromatin structure that includes the recruitment of Polycomb proteins, but it is largely unknown how Xist RNA mediates these processes. To investigate a potential link between the RNAi pathway and X inactivation, we generated and analyzed Dicer-deficient embryonic stem (ES) cells. In the absence of Dicer, coating by Xist RNA, initiation of silencing, and recruitment of Polycomb proteins occur normally. Dicer ablation had modest effects on the steady-state levels of spliced Xist RNA. Together our data indicate that the RNAi machinery is not essential for the initiation of X inactivation.