Rsx is ametatherianRNAwith Xist-like properties in X-chromosome inactivation

• Published in: Nature (London) Vol. 487; no. 7406; p. 254
• Main Authors: Grant, Jennifer, Mahadevaiah, Shantha K, Khil, Pavel, Sangrithi, Mahesh N, Royo, Hélène, Duckworth, Janine, McCarrey, John R, VandeBerg, John L, Renfree, Marilyn B, Taylor, Willie, Elgar, Greg, Camerini-Otero, R Daniel, Gilchrist, Mike J, Turner, James M A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 12-07-2012
• Subjects: Artificial chromosomes; Chromosomes; Comparative studies; Epigenetics; Genes; Genetics; Inactivation; Mammals; Marsupials; Stem cells
• ISSN: 0028-0836; 1476-4687

In female (XX) mammals, one of the two X chromosomes is inactivated to ensure an equal dose of X-linked genes with males (XY)1. X-chromosome inactivation in eutherian mammals is mediated by the non-coding RNA Xist2. Xist is not found in metatherians3 (marsupials), and how X-chromosome inactivation is initiated in these mammals has been the subject of speculation for decades4. Using the marsupial Monodelphis domestica, here we identify Rsx (RNA-on-the-silent X), an RNA that has properties consistent with a role in X-chromosome inactivation. Rsx is a large, repeat-rich RNA that is expressed only in females and is transcribed from, and coats, the inactive X chromosome. In female germ cells, in which both X chromosomes are active, Rsx is silenced, linking Rsx expression to X-chromosome inactivation and reactivation. Integration of an Rsx transgene on an autosome in mouse embryonic stem cells leads to gene silencing in cis. Our findings permit comparative studies of X-chromosome inactivation in mammals and pose questions about the mechanisms by which X-chromosome inactivation is achieved in eutherians. [PUBLICATION ABSTRACT]