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The Long Noncoding RNA, Jpx, Is a Molecular Switch for X Chromosome Inactivation
Ist Teil von
Cell, 2010-10, Vol.143 (3), p.390-403
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2010
Link zum Volltext
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
Once protein-coding, the X-inactivation center (
Xic) is now dominated by large noncoding RNAs (ncRNA). X chromosome inactivation (XCI) equalizes gene expression between mammalian males and females by inactivating one X in female cells. XCI requires Xist, an ncRNA that coats the X and recruits Polycomb proteins. How
Xist is controlled remains unclear but likely involves negative and positive regulators. For the active X, the antisense Tsix RNA is an established
Xist repressor. For the inactive X, here, we identify
Xic-encoded
Jpx as an
Xist activator.
Jpx is developmentally regulated and accumulates during XCI. Deleting
Jpx blocks XCI and is female lethal. Posttranscriptional Jpx knockdown recapitulates the knockout, and supplying Jpx in
trans rescues lethality. Thus,
Jpx is
trans-acting and functions as ncRNA. Furthermore,
ΔJpx is rescued by truncating Tsix, indicating an antagonistic relationship between the ncRNAs. We conclude that
Xist is controlled by two RNA-based switches: Tsix for Xa and Jpx for Xi.
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► X chromosome inactivation is controlled by two RNA-based switches, Jpx and Tsix ► Jpx is a long ncRNA that activates Xist expression ► Tsix RNA opposes the action of Jpx RNA ► Unlike other RNAs of the X-inactivation center, Jpx is diffusible and
trans-acting