在雌性哺乳动物中,两条X染色体需要随机失活一条,以确保雌雄个体有同等剂量的X染色体转录产物。以往的研究中,研究者发现非编码RNAXist介导真哺乳亚纲动物X染色体失活,但在后兽亚纲动物中不存在Xist。因此后兽亚纲动物的X染色体失活机制是什么成为困扰科学界已久的谜题。
本文中,研究者利用短尾猊作为研究对象,发现Rsx (RNA-on-the-silent X) 介导X染色体失活。Rsx只在雌性动物体内表达,它从X染色体上转录,并能够包裹在失活的X染色体上。在雌性动物的生殖细胞中,即两条X染色体都处于活化状态的细胞,Rsx不表达。此外,研究者在小鼠胚胎干细胞中表达Rsx,发现可通过顺式调节引起基因沉默。
该研究阐明了后兽亚纲动物的X染色体沉默机制,是对哺乳动物X染色体沉默机制的有利补充。(生物谷 Bioon.com )
doi:10.1038/nature11171
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Rsx is a metatherian RNA with Xist-like properties in X-chromosome inactivation
Jennifer Grant, Shantha K. Mahadevaiah, Pavel Khil, Mahesh N. Sangrithi, Hélène Royo, Janine Duckworth, John R. McCarrey, John L. VandeBerg, Marilyn B. Renfree, Willie Taylor, Greg Elgar, R. Daniel Camerini-Otero, Mike J. Gilchrist & James M. A. Turner
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.