Human XIST: Origin and Divergence of a <i>cis</i>-Acting Silencing RNA
Dimorphism of sex chromosomes often leads to a need for dosage compensation. In eutherian mammals, XIST, a long non-coding RNA, is expressed from the X chromosome that will be silenced, triggering X-chromosome inactivation (XCI). XIST originated from the ancestral protein-coding <i>Lnx3</i&...
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MDPI AG
2025-05-01
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| author | Maria Jose Navarro-Cobos Carolyn J. Brown |
| author_facet | Maria Jose Navarro-Cobos Carolyn J. Brown |
| author_sort | Maria Jose Navarro-Cobos |
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| description | Dimorphism of sex chromosomes often leads to a need for dosage compensation. In eutherian mammals, XIST, a long non-coding RNA, is expressed from the X chromosome that will be silenced, triggering X-chromosome inactivation (XCI). XIST originated from the ancestral protein-coding <i>Lnx3</i> gene with contributions from various mobile elements that contributed to the striking domains of tandem repeats within the first and sixth exons. Modular domains of XIST are now involved in recruiting heterochromatic marks and proteins essential for XCI initiation and maintenance. This review presents a comparative analysis of human <i>XIST</i> with five other eutherian mammals—chimpanzees, cats, pigs, sheep, and mice—examining conservation across exons as well as the tandem repeats. Notably, repeats exhibited higher conservation than exons, underscoring their functional importance. Additionally, a species-specific G repeat, previously described in pigs, was also identified in sheep and cats. These findings provide insights into the domains of XIST, a <i>cis</i>-acting silencer that has been used to proposed to alleviate the impact of a supernumerary chromosome in Down syndrome. |
| format | Article |
| id | doaj-art-274bb428325540d9ad4e930cecd5a14b |
| institution | DOAJ |
| issn | 2311-553X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Non-Coding RNA |
| spelling | doaj-art-274bb428325540d9ad4e930cecd5a14b2025-08-20T03:16:21ZengMDPI AGNon-Coding RNA2311-553X2025-05-011133510.3390/ncrna11030035Human XIST: Origin and Divergence of a <i>cis</i>-Acting Silencing RNAMaria Jose Navarro-Cobos0Carolyn J. Brown1Department of Medical Genetics, Molecular Epigenetics Group, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, CanadaDepartment of Medical Genetics, Molecular Epigenetics Group, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, CanadaDimorphism of sex chromosomes often leads to a need for dosage compensation. In eutherian mammals, XIST, a long non-coding RNA, is expressed from the X chromosome that will be silenced, triggering X-chromosome inactivation (XCI). XIST originated from the ancestral protein-coding <i>Lnx3</i> gene with contributions from various mobile elements that contributed to the striking domains of tandem repeats within the first and sixth exons. Modular domains of XIST are now involved in recruiting heterochromatic marks and proteins essential for XCI initiation and maintenance. This review presents a comparative analysis of human <i>XIST</i> with five other eutherian mammals—chimpanzees, cats, pigs, sheep, and mice—examining conservation across exons as well as the tandem repeats. Notably, repeats exhibited higher conservation than exons, underscoring their functional importance. Additionally, a species-specific G repeat, previously described in pigs, was also identified in sheep and cats. These findings provide insights into the domains of XIST, a <i>cis</i>-acting silencer that has been used to proposed to alleviate the impact of a supernumerary chromosome in Down syndrome.https://www.mdpi.com/2311-553X/11/3/35XISTXCIlnc-RNAs evolution |
| spellingShingle | Maria Jose Navarro-Cobos Carolyn J. Brown Human XIST: Origin and Divergence of a <i>cis</i>-Acting Silencing RNA Non-Coding RNA XIST XCI lnc-RNAs evolution |
| title | Human XIST: Origin and Divergence of a <i>cis</i>-Acting Silencing RNA |
| title_full | Human XIST: Origin and Divergence of a <i>cis</i>-Acting Silencing RNA |
| title_fullStr | Human XIST: Origin and Divergence of a <i>cis</i>-Acting Silencing RNA |
| title_full_unstemmed | Human XIST: Origin and Divergence of a <i>cis</i>-Acting Silencing RNA |
| title_short | Human XIST: Origin and Divergence of a <i>cis</i>-Acting Silencing RNA |
| title_sort | human xist origin and divergence of a i cis i acting silencing rna |
| topic | XIST XCI lnc-RNAs evolution |
| url | https://www.mdpi.com/2311-553X/11/3/35 |
| work_keys_str_mv | AT mariajosenavarrocobos humanxistoriginanddivergenceofaicisiactingsilencingrna AT carolynjbrown humanxistoriginanddivergenceofaicisiactingsilencingrna |