Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, United States.
Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, United States.
Biochim Biophys Acta Gene Regul Mech. 2017 Mar;1860(3):299-315. doi: 10.1016/j.bbagrm.2016.12.008. Epub 2017 Jan 15.
The multifunctional Survival Motor Neuron (SMN) protein is required for the survival of all organisms of the animal kingdom. SMN impacts various aspects of RNA metabolism through the formation and/or interaction with ribonucleoprotein (RNP) complexes. SMN regulates biogenesis of small nuclear RNPs, small nucleolar RNPs, small Cajal body-associated RNPs, signal recognition particles and telomerase. SMN also plays an important role in DNA repair, transcription, pre-mRNA splicing, histone mRNA processing, translation, selenoprotein synthesis, macromolecular trafficking, stress granule formation, cell signaling and cytoskeleton maintenance. The tissue-specific requirement of SMN is dictated by the variety and the abundance of its interacting partners. Reduced expression of SMN causes spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. SMA displays a broad spectrum ranging from embryonic lethality to an adult onset. Aberrant expression and/or localization of SMN has also been associated with male infertility, inclusion body myositis, amyotrophic lateral sclerosis and osteoarthritis. This review provides a summary of various SMN functions with implications to a better understanding of SMA and other pathological conditions.
多功能运动神经元存活蛋白(SMN)是动物王国所有生物存活所必需的。SMN 通过形成和/或与核糖核蛋白(RNP)复合物相互作用,影响 RNA 代谢的各个方面。SMN 调节小核 RNP、小核仁 RNP、小 Cajal 体相关 RNP、信号识别颗粒和端粒酶的生物发生。SMN 还在 DNA 修复、转录、前体 mRNA 剪接、组蛋白 mRNA 加工、翻译、硒蛋白合成、大分子运输、应激颗粒形成、细胞信号转导和细胞骨架维持中发挥重要作用。SMN 的组织特异性需求由其相互作用伙伴的多样性和丰度决定。SMN 表达减少会导致脊髓性肌萎缩症(SMA),这是婴儿死亡的主要遗传原因。SMA 表现出从胚胎致死到成人发病的广泛范围。SMN 的异常表达和/或定位也与男性不育、包涵体肌炎、肌萎缩侧索硬化症和骨关节炎有关。本综述提供了对各种 SMN 功能的总结,对更好地理解 SMA 和其他病理状况具有重要意义。