Liu Q, Fischer U, Wang F, Dreyfuss G
Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104-6148, USA.
Cell. 1997 Sep 19;90(6):1013-21. doi: 10.1016/s0092-8674(00)80367-0.
Spinal muscular atrophy (SMA), one of the most common fatal autosomal recessive diseases, is characterized by degeneration of motor neurons and muscular atrophy. The SMA disease gene, termed Survival of Motor Neurons (SMN), is deleted or mutated in over 98% of SMA patients. The function of the SMN protein is unknown. We found that SMN is tightly associated with a novel protein, SIP1, and together they form a specific complex with several spliceosomal snRNP proteins. SMN interacts directly with several of the snRNP Sm core proteins, including B, D1-3, and E. Interestingly, SIP1 has significant sequence similarity with Brr1, a yeast protein critical for snRNP biogenesis. These findings suggest a role for SMN and SIP1 in spliceosomal snRNP biogenesis and function and provide a likely molecular mechanism for the cause of SMA.
脊髓性肌萎缩症（SMA）是最常见的致命常染色体隐性疾病之一，其特征为运动神经元变性和肌肉萎缩。SMA疾病基因，即运动神经元存活基因（SMN），在超过98%的SMA患者中存在缺失或突变。SMN蛋白的功能尚不清楚。我们发现SMN与一种新蛋白SIP1紧密相关，并且它们共同与几种剪接体snRNP蛋白形成一种特定复合物。SMN直接与几种snRNP Sm核心蛋白相互作用，包括B、D1 - 3和E。有趣的是，SIP1与Brr1具有显著的序列相似性，Brr1是一种对snRNP生物合成至关重要的酵母蛋白。这些发现表明SMN和SIP1在剪接体snRNP生物合成和功能中发挥作用，并为SMA的病因提供了一种可能的分子机制。
