Intersection of the RNA interference and X-inactivation pathways
Intersection of the RNA interference and X-inactivation pathways
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DOI：
10.1126/science.1157676
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发表时间：
2008-06-06
期刊：
影响因子：
56.9
通讯作者：
Lee, Jeannie T.
中科院分区：
文献类型：
--
作者：
Ogawa, Yuya;Sun, Bryan K.;Lee, Jeannie T.
在哺乳动物中，剂量补偿是通过雌性X染色体失活（XCI）实现的。非编码Xist基因启动X染色体的沉默，而其反义配偶体Tsix阻断沉默。Xist和Tsix RNA的互补性长期以来一直表明RNA干扰（RNAi）的作用。在这里，我们报告说，小鼠Xist和Tsix形式的双链体在体内。在XCI期间，双链体被加工成小RNA（sRNA），最可能以Dicer依赖性方式在活性X（Xa）上。删除Dicer会损害sRNA的产生并使Xist去抑制。此外，在没有Dicer的情况下，Xist RNA不能积累，并且组蛋白3赖氨酸27三甲基化在无活性的X（Xi）上被阻断。通过截断Tsix来部分挽救缺陷。因此，XCI和RNAi交叉，下调Xa上的Xist并在Xi上传播沉默。
In mammals, dosage compensation is achieved by X- chromosome inactivation ( XCI) in the female. The noncoding Xist gene initiates silencing of the X chromosome, whereas its antisense partner Tsix blocks silencing. The complementarity of Xist and Tsix RNAs has long suggested a role for RNA interference ( RNAi). Here, we report that murine Xist and Tsix form duplexes in vivo. During XCI, the duplexes are processed to small RNAs ( sRNAs), most likely on the active X ( Xa) in a Dicer- dependent manner. Deleting Dicer compromises sRNA production and derepresses Xist. Furthermore, without Dicer, Xist RNA cannot accumulate and histone 3 lysine 27 trimethylation is blocked on the inactive X ( Xi). The defects are partially rescued by truncating Tsix. Thus, XCI and RNAi intersect, down- regulating Xist on Xa and spreading silencing on Xi.