在雌性哺乳動(dòng)物中,,兩條X染色體需要隨機(jī)失活一條,,以確保雌雄個(gè)體有同等劑量的X染色體轉(zhuǎn)錄產(chǎn)物,。以往的研究中,,研究者發(fā)現(xiàn)非編碼RNAXist介導(dǎo)真哺乳亞綱動(dòng)物X染色體失活,,但在后獸亞綱動(dòng)物中不存在Xist。因此后獸亞綱動(dòng)物的X染色體失活機(jī)制是什么成為困擾科學(xué)界已久的謎題,。
本文中,,研究者利用短尾猊作為研究對(duì)象,發(fā)現(xiàn)Rsx (RNA-on-the-silent X) 介導(dǎo)X染色體失活,。Rsx只在雌性動(dòng)物體內(nèi)表達(dá),,它從X染色體上轉(zhuǎn)錄,并能夠包裹在失活的X染色體上,。在雌性動(dòng)物的生殖細(xì)胞中,,即兩條X染色體都處于活化狀態(tài)的細(xì)胞,Rsx不表達(dá),。此外,,研究者在小鼠胚胎干細(xì)胞中表達(dá)Rsx,發(fā)現(xiàn)可通過(guò)順式調(diào)節(jié)引起基因沉默,。
該研究闡明了后獸亞綱動(dòng)物的X染色體沉默機(jī)制,,是對(duì)哺乳動(dòng)物X染色體沉默機(jī)制的有利補(bǔ)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.