Whittom A A, Xu H, Hebert M D
Department of Biochemistry, The University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
Cell Mol Life Sci. 2008 Apr;65(7-8):1256-71. doi: 10.1007/s00018-008-7587-3.
Cajal bodies (CBs) and Gems are nuclear domains that contain factors responsible for spliceosomal small nuclear ribonucleoprotein (snRNP) biogenesis. The marker protein for CBs is coilin. In addition to snRNPs, coilin and other factors, canonical CBs contain the survivor of motor neuron protein (SMN). SMN can also localize to Gems. Considering the important role that coilin plays in the formation and composition of CBs, we tested the splicing efficiency of several cell lines that vary in regards to coilin level and modification using an artificial reporter substrate. We found that cells with both hypomethylated coilin and Gems are more efficient at reporter splicing compared to cells in which SMN localizes to CBs. In contrast, coilin reduction, which induces Gem formation, decreases cell proliferation and artificial reporter splicing. These findings demonstrate that coilin modifications or levels impact artificial reporter splicing, possibly by influencing snRNP biogenesis.
卡哈尔体(CBs)和宝石样小体是细胞核结构域,其中含有负责剪接体小核核糖核蛋白(snRNP)生物合成的因子。CBs的标记蛋白是卷曲螺旋蛋白。除了snRNPs、卷曲螺旋蛋白和其他因子外,典型的CBs还含有运动神经元存活蛋白(SMN)。SMN也可定位于宝石样小体。鉴于卷曲螺旋蛋白在CBs的形成和组成中发挥的重要作用,我们使用人工报告底物测试了几种卷曲螺旋蛋白水平和修饰情况不同的细胞系的剪接效率。我们发现,与SMN定位于CBs的细胞相比,卷曲螺旋蛋白低甲基化且存在宝石样小体的细胞在报告基因剪接方面效率更高。相反,诱导宝石样小体形成的卷曲螺旋蛋白减少会降低细胞增殖和人工报告基因剪接。这些发现表明,卷曲螺旋蛋白的修饰或水平可能通过影响snRNP生物合成来影响人工报告基因剪接。