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.
Department of Molecular Biology, Massachusetts General Hospital and Howard Hughes Medical Institute, Boston, MA 02114, USA.
Yuya
Y
Ogawa
Bryan K
BK
Sun
Jeannie T
JT
Lee
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D005260:Female; D006657:Histones / Q000378:metabolism; D008297:Male; D008745:Methylation; D051379:Mice; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000378:metabolism; D062085:RNA, Long Noncoding; D012342:RNA, Small Nuclear / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043244:Ribonuclease III; D014960:X Chromosome / Q000235:genetics* / Q000378:metabolism; D049951:X Chromosome Inactivation
D006657:Histones; D012330:RNA, Double-Stranded; D062085:RNA, Long Noncoding; D012342:RNA, Small Nuclear; D022661:RNA, Untranslated; C465658:Tsix transcript, mouse; C077885:XIST non-coding RNA; D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases