Xist Exon 7 Contributes to the Stable Localization of Xist RNA on the Inactive X-Chromosome

To equalize x-linked gene dosage between the sexes in mammalian females,xist rna inactivates one of the two x-chromosomes. here,we report the crucial function of xist exon 7 in x-inactivation. xist exon 7 is the second-largest exon with a well-conserved repeat e in eutherian mammals,but its role is often overlooked in x-inactivation. although female es cells with a targeted truncation of the xist exon 7 showed no significant differences in their xist expression levels and rna stability from control cells expressing wild-type xist,compromised localization of xist rna and incomplete silencing of x-linked genes on the inactive x-chromosome (xi) were observed in the exon 7-truncated mutant cells. furthermore,the interaction between the mutant xist rna and hnrnp u required for localization of xist rna to the xi was impaired in the xist exon 7 truncation mutant cells. our results suggest that exon 7 of xist rna plays an important role for stable xist rna localization and silencing of the x-linked genes on the xi,possibly acting through an interaction with hnrnp u. © 2015 yamada et al.