Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, and Brain Center, Zhongnan Hospital, Wuhan University, China.
Taihe Hospital, Hubei University of Medicine, Shiyan, China.
FEBS Lett. 2018 Apr;592(8):1400-1411. doi: 10.1002/1873-3468.13031. Epub 2018 Apr 10.
Gemin5 acts as a U1 small nuclear RNA (snRNA)-binding protein in U1 small nuclear ribonucleic protein (snRNP) biogenesis. Here, we report a role for Gemin5 in unassembled U1 snRNP disposal under survival of motor neuron (SMN) protein-deficient conditions. We demonstrate that non-Sm protein-associated U1 snRNA and U1A are enriched in cytoplasmic granules and colocalize to P bodies in SMN-deficient cells. Immunoprecipitation assays show increased associations of the U1 snRNP component U1A with P body components and Gemin5 in SMN-deficient cells. More importantly, Gemin5 knockdown eliminates the unassembled U1 snRNP granules and rescues U1 snRNA levels in SMN-deficient cells. Taken together, our study provides direct evidence that Gemin5 is involved in unassembled-U1 snRNA disposal under conditions of SMN deficiency.
Gemin5 作为 U1 小核 RNA（snRNA）-结合蛋白在 U1 小核核糖核蛋白（snRNP）生物发生中起作用。在这里，我们报告了 Gemin5 在运动神经元存活蛋白（SMN）缺乏条件下未组装的 U1 snRNP 处置中的作用。我们证明了非 Sm 蛋白相关的 U1 snRNA 和 U1A 在 SMN 缺乏的细胞中富含细胞质颗粒，并与 P 体共定位。免疫沉淀试验显示，在 SMN 缺乏的细胞中，U1 snRNP 成分 U1A 与 P 体成分和 Gemin5 的结合增加。更重要的是，Gemin5 的敲低消除了未组装的 U1 snRNP 颗粒，并挽救了 SMN 缺乏的细胞中的 U1 snRNA 水平。总之，我们的研究提供了直接证据，表明 Gemin5 参与了 SMN 缺乏条件下未组装的 U1 snRNA 的处理。
