title: Xist Exon 7 Contributes to the Stable Localization of Xist RNA on the Inactive X-Chromosome.
abstract: 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.
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
authors.forename: Norishige
authors.initials: N
authors.lastname: Yamada
authors.affiliation: RNA Biology Laboratory, RIKEN Advanced Research Institute, Wako, Saitama, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
authors.forename: Minghui
authors.initials: M
authors.lastname: Yue
authors.affiliation: Department of Oral Surgery, Kagoshima University Hospital, Kagoshima, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Hamada
authors.affiliation: RNA Biology Laboratory, RIKEN Advanced Research Institute, Wako, Saitama, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nakagawa
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D058732:Embryoid Bodies / Q000502:physiology; D005091:Exons; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D008297:Male; D051379:Mice; D034443:RNA Transport; D062085:RNA, Long Noncoding / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics*; D049951:X Chromosome Inactivation
chemical_list: D062085:RNA, Long Noncoding; C077885:XIST non-coding RNA