*VIB Center for the Biology of Disease and Center for Human Genetics, KU Leuven, 3000 Leuven, Belgium.
Biochem Soc Trans. 2013 Dec;41(6):1593-7. doi: 10.1042/BST20130142.
MNDs (motor neuron diseases) form a heterogeneous group of pathologies characterized by the progressive degeneration of motor neurons. More and more genetic factors associated with MND encode proteins that have a function in RNA metabolism, suggesting that disturbed RNA metabolism could be a common underlying problem in several, perhaps all, forms of MND. In the present paper we review recent developments showing a functional link between SMN (survival of motor neuron), the causative factor of SMA (spinal muscular atrophy), and FUS (fused in sarcoma), a genetic factor in ALS (amyotrophic lateral sclerosis). SMN is long known to have a crucial role in the biogenesis and localization of the spliceosomal snRNPs (small nuclear ribonucleoproteins), which are essential assembly modules of the splicing machinery. Now we know that FUS interacts with SMN and pathogenic FUS mutations have a significant effect on snRNP localization. Together with other recently published evidence, this finding potentially links ALS pathogenesis to disturbances in the splicing machinery, and implies that pre-mRNA splicing may be the common weak point in MND, although other steps in mRNA metabolism could also play a role. Certainly, further comparison of the RNA metabolism in different MND will greatly help our understanding of the molecular causes of these devastating diseases.
运动神经元疾病（MNDs）是一组异质性的病理学，其特征是运动神经元的进行性退化。越来越多与 MND 相关的遗传因素编码在 RNA 代谢中具有功能的蛋白质，这表明 RNA 代谢紊乱可能是几种（也许是所有）MND 形式的共同潜在问题。在本文中，我们回顾了最近的研究进展，这些进展表明运动神经元存活（SMN），即脊髓性肌萎缩症（SMA）的致病因素，与 FUS（肉瘤中融合）之间存在功能联系，FUS 是肌萎缩侧索硬化症（ALS）的遗传因素。SMN 长期以来一直被认为在剪接体 snRNPs（小核核糖核蛋白）的生物发生和定位中具有关键作用，snRNPs 是剪接机制的基本组装模块。现在我们知道 FUS 与 SMN 相互作用，致病性 FUS 突变对 snRNP 定位有显著影响。结合其他最近发表的证据，这一发现可能将 ALS 的发病机制与剪接机制的紊乱联系起来，并暗示在 MND 中，前体 mRNA 剪接可能是共同的薄弱环节，尽管 mRNA 代谢的其他步骤也可能起作用。当然，对不同 MND 中的 RNA 代谢进行进一步比较将极大地帮助我们理解这些毁灭性疾病的分子原因。
