Spinal muscular atrophy (SMA) is a devastating motor neuron disorder caused by mutations in the survival motor neuron (SMN) gene. It remains unclear how SMN deficiency leads to the loss of motor neurons. By screening Schizosaccharomyces pombe, we found that the growth defect of an SMN mutant can be alleviated by deletion of the actin-capping protein subunit gene acp1⁺. We show that SMN mutated cells have splicing defects in the profilin gene, which thus directly hinder actin cytoskeleton homeostasis including endocytosis and cytokinesis. We conclude that deletion of acp1⁺ in an SMN mutant background compensates for actin cytoskeleton alterations by restoring redistribution of actin monomers between different types of cellular actin networks. Our data reveal a direct correlation between an impaired function of SMN in snRNP assembly and defects in actin dynamics. They also point to important common features in the pathogenic mechanism of SMA and ALS.

脊髓性肌萎缩症（SMA）是一种毁灭性运动神经元疾病，由存活运动神经元（SMN）基因突变引起。尚不清楚SMN缺乏如何导致运动神经元的丢失。通过筛选粟酒裂殖酵母，我们发现SMN突变体的生长缺陷可以通过删除肌动蛋白封端蛋白亚基基因acp1 ⁺来缓解。我们显示，SMN突变的细胞在profilin基因中具有剪接缺陷，从而直接阻碍肌动蛋白细胞骨架的稳态，包括内吞作用和胞质分裂。我们得出结论，删除acp1 ⁺在SMN突变体中，通过恢复肌动蛋白单体在不同类型的细胞肌动蛋白网络之间的重新分布，可以补偿肌动蛋白的细胞骨架改变。我们的数据揭示了SMR在snRNP装配中受损的功能与肌动蛋白动力学缺陷之间的直接相关性。他们还指出了SMA和ALS的致病机制中的重要共同特征。