Tsx produces a long noncoding RNA and has general functions in the germline, stem cells, and brain.
Tsx produces a long noncoding RNA and has general functions in the germline, stem cells, and brain.
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DOI：
10.1371/journal.pgen.1002248
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发表时间：
2011-09
期刊：
影响因子：
4.5
通讯作者：
Lee JT
中科院分区：
文献类型：
--
作者：
Anguera MC;Ma W;Clift D;Namekawa S;Kelleher RJ 3rd;Lee JT
Tsx基因位于X失活中心，被认为编码一种在睾丸中表达的蛋白质，但其功能仍然是个谜。鉴于其接近非编码基因，调节X-失活，在这里，我们的特点Tsx，并确定其在小鼠中的功能。我们发现Tsx实际上是非编码的，并且长转录本在减数分裂生殖细胞、胚胎干细胞和大脑中强烈表达。Tsx的靶向缺失会产生可存活的后代，而X失活在胚胎干细胞中仅受到轻微影响。然而，突变的胚胎干细胞严重生长迟缓，分化差，并显示出升高的细胞死亡。此外，雄性小鼠睾丸较小，这是由于粗面素特异性细胞凋亡和母体特异性效应导致窝仔略小。有趣的是，缺乏Tsx的雄性小鼠不那么害怕，并且海马体的短期记忆明显增强。结合，我们的研究表明，Tsx在多种细胞类型中执行一般功能，并将非编码基因座与哺乳动物的干细胞和生殖细胞发育，学习和行为联系起来。X连锁基因Tsx位于X失活中心，被认为编码一种在睾丸中表达的蛋白，但其功能尚不清楚。在这里，我们表明Tsx实际上是一个非编码RNA，一个新成员的大非编码RNA家族表达的X。Tsx在减数分裂生殖细胞、胚胎干细胞和脑中大量表达。Tsx的靶向缺失产生了可存活的后代，窝仔比小于预期，X失活受到轻度影响（在胚胎干细胞中），雄性动物由于生殖细胞凋亡而具有较小的睾丸。突变的胚胎干细胞严重生长迟缓，分化不良，细胞死亡增加。这种非编码RNA的缺失改变了小鼠的行为，动物表现出更少的恐惧和增强的短期记忆。我们的研究表明，Tsx在多种细胞类型中执行一般功能，并将非编码位点与哺乳动物的干细胞和生殖细胞发育，学习和行为联系起来。
The Tsx gene resides at the X-inactivation center and is thought to encode a protein expressed in testis, but its function has remained mysterious. Given its proximity to noncoding genes that regulate X-inactivation, here we characterize Tsx and determine its function in mice. We find that Tsx is actually noncoding and the long transcript is expressed robustly in meiotic germ cells, embryonic stem cells, and brain. Targeted deletion of Tsx generates viable offspring and X-inactivation is only mildly affected in embryonic stem cells. However, mutant embryonic stem cells are severely growth-retarded, differentiate poorly, and show elevated cell death. Furthermore, male mice have smaller testes resulting from pachytene-specific apoptosis and a maternal-specific effect results in slightly smaller litters. Intriguingly, male mice lacking Tsx are less fearful and have measurably enhanced hippocampal short-term memory. Combined, our study indicates that Tsx performs general functions in multiple cell types and links the noncoding locus to stem and germ cell development, learning, and behavior in mammals. The X-linked gene Tsx is located within the X-inactivation center and is thought to encode a protein expressed in testis, yet its function is not known. Here we show that Tsx is actually a noncoding RNA, a new member of the large noncoding RNA family expressed from the X. Tsx is abundantly expressed in meiotic germ cells, embryonic stem cells, and brain. Targeted deletion of Tsx generates viable offspring, litter ratios are smaller than expected, X-inactivation is mildly affected (in embryonic stem cells), and male animals have smaller testes due to germ cell apoptosis. Mutant embryonic stem cells are severely growth-retarded and differentiate poorly with elevated cell death. Deletion of this noncoding RNA alters mouse behavior, with animals displaying less fear and enhanced short-term memory. Our study indicates that Tsx performs general functions in multiple cell types and links the noncoding locus to stem and germ cell development, learning, and behavior in mammals.
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