Navarro-Cobos Maria Jose, Brown Carolyn J
Department of Medical Genetics, Molecular Epigenetics Group, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
Noncoding RNA. 2025 May 1;11(3):35. doi: 10.3390/ncrna11030035.
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 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 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 -acting silencer that has been used to proposed to alleviate the impact of a supernumerary chromosome in Down syndrome.
性染色体的二态性常常导致剂量补偿的需求。在真兽亚纲哺乳动物中，一种长链非编码RNA——XIST，从将被沉默的X染色体上表达，从而引发X染色体失活（XCI）。XIST起源于祖先的蛋白质编码基因，多种移动元件对其有贡献，这些元件促成了第一和第六外显子内串联重复序列的显著结构域。XIST的模块化结构域现在参与招募异染色质标记以及XCI起始和维持所必需的蛋白质。本综述对人类与其他五种真兽亚纲哺乳动物——黑猩猩、猫、猪、绵羊和小鼠——进行了比较分析，研究了外显子以及串联重复序列的保守性。值得注意的是，重复序列的保守性高于外显子，这突出了它们的功能重要性。此外，先前在猪中描述的一种物种特异性G重复序列，在绵羊和猫中也被发现。这些发现为XIST的结构域提供了见解，XIST是一种反式作用沉默子，有人提出它可用于减轻唐氏综合征中额外染色体的影响。
