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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >SMN mutants of spinal muscular atrophy patients are defective in hinding to snRNP proteins
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SMN mutants of spinal muscular atrophy patients are defective in hinding to snRNP proteins

机译：脊髓性肌萎缩症患者的SMN突变体在阻碍snRNP蛋白方面存在缺陷

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摘要

Spinal muscular atrophy (SMA) is a com- mon motor neuron degenerative disease and the leading senetic cause of death of young children. The survival of motor neurons (SMN)gene, the SMA disease gene, is homozygously deleted or mutated in more than 98 of SMA patients. The SMN protein interacts with itself, with SMN-interacting protein l, and with several spliceosomal small nuclear ribo- nucleoprotein (snRNP) Sm proteins. A complex containing SMN plays a critical role in spliceosomal snRNP assembly and in pre-mRNA splicing. SMN mutants found in SMA patients show reduced selfassociation and lack the capacity to regen- erate the splicing machinery. Here we demonstrate that SMN mutants found in SMA patients are defective in binding to Sm proteins. Morcover, we show that SMN, but not mutants found in SMA patients, can form large oligomers and that SMN oligomerization is required for high-affinity binding to spli- ceosomal snRNP Sm proteins. These findings directly link the impaired interaction between SMN and Sm proteins to a defect in snRNP metabolism and to SMA.
机译：脊髓性肌萎缩症（SMA）是一种常见的运动神经元退化性疾病，也是导致幼儿死亡的主要感官原因。运动神经元（SMN）基因（SMA疾病基因）的存活在98多个SMA患者中被纯合缺失或突变。 SMN蛋白与自身，与SMN相互作用的蛋白1以及几种剪接小核糖核糖核蛋白（snRNP）Sm蛋白相互作用。含有SMN的复合体在剪接体snRNP组装和mRNA剪接中起着至关重要的作用。在SMA患者中发现的SMN突变体显示出自缔合减少，并且缺乏再生剪接机制的能力。在这里，我们证明在SMA患者中发现的SMN突变体在结合Sm蛋白方面存在缺陷。 Morcover，我们表明SMN可以形成大的寡聚体，但不能在SMA患者中发现突变体，并且SMN寡聚化是高亲和力结合于SnRNP Sm蛋白的必要条件。这些发现直接将SMN和Sm蛋白之间相互作用的减弱与snRNP代谢缺陷和SMA联系起来。

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