Kapeli Katannya, Martinez Fernando J, Yeo Gene W
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117593, Singapore.
Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, 92093, USA.
Hum Genet. 2017 Sep;136(9):1193-1214. doi: 10.1007/s00439-017-1830-7. Epub 2017 Jul 31.
Mutations in genes that encode RNA-binding proteins (RBPs) have emerged as critical determinants of neurological diseases, especially motor neuron disorders such as amyotrophic lateral sclerosis (ALS). RBPs are involved in all aspects of RNA processing, controlling the life cycle of RNAs from synthesis to degradation. Hallmark features of RBPs in neuron dysfunction include misregulation of RNA processing, mislocalization of RBPs to the cytoplasm, and abnormal aggregation of RBPs. Much progress has been made in understanding how ALS-associated mutations in RBPs drive pathogenesis. Here, we focus on several key RBPs involved in ALS-TDP-43, HNRNP A2/B1, HNRNP A1, FUS, EWSR1, and TAF15-and review our current understanding of how mutations in these proteins cause disease.
编码RNA结合蛋白（RBP）的基因突变已成为神经疾病的关键决定因素，尤其是运动神经元疾病，如肌萎缩侧索硬化症（ALS）。RBP参与RNA加工的各个方面，控制RNA从合成到降解的生命周期。RBP在神经元功能障碍中的标志性特征包括RNA加工失调、RBP错误定位到细胞质以及RBP异常聚集。在理解RBP中与ALS相关的突变如何驱动发病机制方面已经取得了很大进展。在这里，我们重点关注几种与ALS相关的关键RBP——TDP-43、HNRNP A2/B1、HNRNP A1、FUS、EWSR1和TAF15，并回顾我们目前对这些蛋白质中的突变如何导致疾病的理解。
