Paushkin Sergey, Gubitz Amélie K, Massenet Séverine, Dreyfuss Gideon
Howard Hughes Medical Institute, and the Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6148, USA.
Curr Opin Cell Biol. 2002 Jun;14(3):305-12. doi: 10.1016/s0955-0674(02)00332-0.
Spinal muscular atrophy is a common, often lethal, neurodegenerative disease that results from low levels of, or loss-of-function mutations in, the SMN (survival of motor neurons) protein. SMN oligomerizes and forms a stable complex with five additional proteins: Gemins 2-6. SMN also interacts with several additional proteins referred to as "substrates". Most of these substrates contain a domain enriched in arginine and glycine residues (the RG-rich domain), and are constituents of different ribonucleoprotein complexes. Recent studies revealed that the substrates can be modified by an arginine methyltransferase complex, the methylosome. This forms symmetrical dimethylarginines within the RG-rich domains of the substrates, thereby converting them to high-affinity binders of the SMN complex, and most likely providing regulation of the ribonucleoprotein assembly processes.
脊髓性肌萎缩症是一种常见的、通常致命的神经退行性疾病,由运动神经元存活蛋白(SMN)水平低或功能丧失突变引起。SMN会寡聚化,并与另外五种蛋白质形成稳定的复合物:Gemins 2 - 6。SMN还与几种被称为“底物”的其他蛋白质相互作用。这些底物中的大多数都含有一个富含精氨酸和甘氨酸残基的结构域(富含RG的结构域),并且是不同核糖核蛋白复合物的组成成分。最近的研究表明,这些底物可被一种精氨酸甲基转移酶复合物——甲基osome修饰。这会在底物的富含RG的结构域内形成对称二甲基精氨酸,从而将它们转化为SMN复合物的高亲和力结合物,并很可能对核糖核蛋白组装过程进行调控。