Tra2betal regulates P19 neuronal differentiation and the splicing of FGF-2R and GluR-B minigenes

The present study demonstrates that the expression of Tra2beta1 (Transformer 2-beta1) proteins, an SR (serine/arginine rich) protein, is developmentally up-regulated in a neural-specific pattern. The up-regulation is also observed in RA (retinoic acid) induced neural differentiation of P19 cells. Tra2betal proteins are located in the nuclei of P19 cells, which are consistent with its functional site as an SR protein. The over-expression of Tra2betal proteins promotes RA induced neuronal differentiation of P19 cells. In P19 cells, the splicing of FGF-2R (fibroblast growth factor receptor 2) minigene produces the BEK form, while the alternative splicing of GluR-B (glutamate receptor subunit B) minigene generates two products, the Flop and the Truncated isoforms. Tra2betal inhibits the BEK splicing, but it promotes the Flop splicing. The results therefore suggest that Tra2betal is involved in the regulation of alternative splicing processes during neural development, peculiarly the splicing of FGF-2R and GluR-B genes. Both FGF-2R and GluR-B genes are known to play important roles in neural differentiation.     

Tra2β1蛋白在神经特异性的基因剪接中的功能

体外(in vitro)生化研究已证明哺乳动物Tra2蛋白是前体mRNA剪接的重要调控因子,但是,对该蛋白在in vivo条件下的剪接功能,尤其是在神经特异性基因剪接中的功能及其细胞特异性,目前所知甚少。本文采用in vivo分析模型,在COS-l和PFSK两种不同类型的细胞中,研究了两个神经特异性基因(GluR-B,SMN2)剪接的细胞特异性,同时分析了Tra2β1在这两个基因剪接中的功能及其细胞特异性。结果表明,在研究的两种细胞中,GluR-B和SMN2“小基因”的剪接均具有明显的细胞特异性;而Tra2β1蛋白的过量表达在这两种不同的细胞中对“小基因”的剪接有显著的相同倾向的调节作用,提示Tra2β1蛋白对该两个基因剪接的调节作用可能没有细胞特异性。     

钠-氢交换蛋白 mRNA在人胎儿两个发育阶段中的组织特异性表达

钠－氢交换蛋白（Na^ -H^ exchangers,NHE）至少包含6个不同的亚型,生长因子可激活其表达。目前,对在发育过程中NHE的表达了解甚少。本文利用RT－PCR观察了4种NHE亚型的mRNA在人胎儿的两个不同发育阶段（11周、16周）在不同组织中的表达,以研究它们的发育调控。结果显示,NHE1 mRNA在两种胎龄的多种组织中均有表达,和16周胚胎相比,11周的胚胎的NHE1 mRNA的表达较弱,并且表现出明显的组织差异。据此推测,NHE1的管家（house-keeping）功能可能至少在11周就开始形成,而最迟在16周已基本建立;NHE2和NHE3 mRNA在11周和16周的胚胎组织中的特异性表达呈现相反的变化趋势及组织分布上的重叠,后者与NHE2和NHE3在成人组织中的分布及功能的重叠的特点相吻合;NHE5 mRNA的表达在11周的胚胎组织中比较普遍,而在16周的胚胎组织中则局限在小脑组织中,本研究表明,在人胚胎发育11－16周期间,NHE的组织特异性表达表现出时间依赖性的调控,而在不迟于胚胎发育的第16周,具有“管家功能”的NHE1的基因表达已与成人相似。