Unleashing XIST from X-chromosome inactivation

Recognition that the most abundant class of genes present in the human genome are those producing long noncoding RNA (lncRNA) has hyped research on this category of transcripts. One such prototypical RNA, Xist, has particularly fueled interest. Initially characterized for its specific expression from the inactive X (Xi), recent studies have uncovered the molecular mechanisms underlying its essential role in the initiation of X-chromosome inactivation, from its exquisitely precise transcriptional regulation to the plethora of protein interactors forming the Xist ribonucleoprotein (RNP) that mediate its gene silencing activity. Here, we will discuss the recent advances that have broadened our knowledge of Xist functions, challenging classical models and revealing unsuspected, unconventional actions of its RNP.