Beyond sense: the role of antisense RNA in controlling Xist expression

The Xist RNA is a critical component of X inactivation, and Tsix is a non-coding antisense RNA to the Xist gene. We review the data from mouse that demonstrates that Tsix serves to regulate Xist expression. TSIX antisense transcripts have also been detected in humans, but without a manipulatable system to study the inactivation process in humans it remains unknown whether these antisense transcripts are functional in regulating human XIST. After a review of the differences between the human and mouse antisense, we discuss how the question of whether or not the human TSIX is functional impacts models of Tsix function.