Intersection of the RNA interference and X-inactivation pathways

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.