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首页> 外文期刊>Biology Open >Gemin4 is an essential gene in mice, and its overexpression in human cells causes relocalization of the SMN complex to the nucleoplasm
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Gemin4 is an essential gene in mice, and its overexpression in human cells causes relocalization of the SMN complex to the nucleoplasm

机译：Gemin4是小鼠的必需基因，其在人细胞中的过度表达导致SMN复合物重新定位于核质

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Gemin4 is a member of the Survival Motor Neuron (SMN) protein complex, which is responsible for the assembly and maturation of Sm-class small nuclear ribonucleoproteins (snRNPs). In metazoa, Sm snRNPs are assembled in the cytoplasm and subsequently imported into the nucleus. We previously showed that the SMN complex is required for snRNP importin vitro, although it remains unclear which specific components direct this process. Here, we report that Gemin4 overexpression drives SMN and the other Gemin proteins from the cytoplasm into the nucleus. Moreover, it disrupts the subnuclear localization of the Cajal body marker protein, coilin, in a dose-dependent manner. We identified three putative nuclear localization signal (NLS) motifs within Gemin4, one of which is necessary and sufficient to direct nuclear import. Overexpression of Gemin4 constructs lacking this NLS sequestered Gemin3 and, to a lesser extent Gemin2, in the cytoplasm but had little effect on the nuclear accumulation of SMN. We also investigated the effects of Gemin4 depletion in the laboratory mouse,Mus musculus.Gemin4null mice die early in embryonic development, demonstrating that Gemin4 is an essential mammalian protein. When crossed onto a severe SMA mutant background, heterozygous loss ofGemin4failed to modify the early postnatal mortality phenotype of SMA type I (Smn?/?;SMN2+/+) mice. We conclude that Gemin4 plays an essential role in mammalian snRNP biogenesis, and may facilitate import of the SMN complex (or subunits thereof) into the nucleus.
机译：Gemin4是Survival Motor Neuron（SMN）蛋白复合物的成员，该复合物负责Sm类小核核糖核蛋白（snRNPs）的组装和成熟。在后生动物中，Sm snRNPs在细胞质中组装，然后导入细胞核。我们先前表明，SMN复合物是体外snRNP导入所必需的，尽管目前尚不清楚哪些特定成分指导该过程。在这里，我们报道Gemin4过表达将SMN和其他Gemin蛋白从细胞质推入细胞核。此外，它以剂量依赖的方式破坏了Cajal身体标志物蛋白线圈蛋白的亚核定位。我们在Gemin4中鉴定出三个假定的核定位信号（NLS）图案，其中之一对于引导核输入是必要且足够的。缺少这种NLS的Gemin4构建体的过表达在细胞质中螯合了Gemin3，在较小程度上隔离了Gemin2，但对SMN的核蓄积影响很小。我们还研究了Gemin4耗竭对实验小鼠小家鼠的影响.Gemin4null小鼠在胚胎发育早期死亡，表明Gemin4是必需的哺乳动物蛋白。当与严重的SMA突变体背景杂交时，Gemin4的杂合丢失无法改变SMA I型（Smn？/ ?; SMN2 + / +）小鼠的早期产后死亡率表型。我们得出的结论是，Gemin4在哺乳动物的snRNP生物发生中起着至关重要的作用，并且可能促进SMN复合物（或其亚基）导入细胞核。

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