Coilin is the main component of Cajal body (CB), a membraneless organelle that is involved in the biogenesis of ribonucleoproteins and telomerase, cell cycle, and cell growth. The disruption of CBs is linked to neurodegenerative diseases and potentially cancers. The coilin gene (COIL) contains two nonsynonymous SNPs: rs116022828 (E121K) and rs61731978 (V145I). Here, we investigated for the first time the functional impacts of these coilin SNPs on CB formation, coilin subcellular localization, microtubule formation, cell growth, and coilin expression and protein structure. We revealed that both E121K and V145I mutants could disrupt CB formation and result in various patterns of subcellular localization with survival motor neuron protein. Noteworthy, many of the E121K cells showed nucleolar coilin accumulation. The microtubule regrowth and cell cycle assays indicated that the E121K cells appeared to be trapped in the S and G2/M phases of cell cycle, resulting in reduced cell proliferation. In silico protein structure prediction suggested that the E121K mutation caused greater destabilization on the coilin structure than the V145I mutation. Additionally, clinical bioinformatic analysis indicated that coilin expression levels could be a risk factor for cancer, depending on the cancer types and races.

中文翻译：

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Coilin 非同义 SNP 变体 E121K 和 V145I 对细胞生长和 Cajal 体形成的影响：首次表征

Coilin 是 Cajal 体 (CB) 的主要成分，CB 是一种无膜细胞器，参与核糖核蛋白和端粒酶的生物发生、细胞周期和细胞生长。CB 的破坏与神经退行性疾病和潜在的癌症有关。卷曲蛋白基因 (COIL) 包含两个非同义 SNP：rs116022828 (E121K) 和 rs61731978 (V145I)。在这里，我们第一次研究了这些卷曲蛋白 SNP 对 CB 形成、卷曲蛋白亚细胞定位、微管形成、细胞生长以及卷曲蛋白表达和蛋白质结构的功能影响。我们发现 E121K 和 V145I 突变体都可以破坏 CB 的形成并导致运动神经元存活蛋白的亚细胞定位的各种模式。值得注意的是，许多 E121K 细胞显示出核仁卷曲蛋白积累。微管再生和细胞周期测定表明 E121K 细胞似乎被困在细胞周期的 S 和 G2/M 期，导致细胞增殖减少。计算机蛋白质结构预测表明，与 V145I 突变相比，E121K 突变对卷曲蛋白结构造成更大的不稳定。此外，临床生物信息学分析表明，coilin 表达水平可能是癌症的危险因素，具体取决于癌症类型和种族。