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.
At a glance
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- Supplementary Information (6.2M)
This file contains Supplementary Figures 1-4, a Supplementary Discussion and additional references.
- Supplementary Table (46K)
This file contains the probe and primer sequences used in this study.
- Supplementary Table 2 (135K)
This file contains the female:male ratios for X-encoded transcripts derived from RNA-seq data.
- Supplementary Table 3 (13K)
This file contains the Australasian marsupial Rsx EST identifiers.