Center for NeuroGenetics, Department of Molecular Genetics and Microbiology, Genetics Institute, and McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, Florida 32610, USA; email:
Annu Rev Neurosci. 2019 Jul 8;42:227-247. doi: 10.1146/annurev-neuro-070918-050405. Epub 2019 Mar 25.
Microsatellite mutations involving the expansion of tri-, tetra-, penta-, or hexanucleotide repeats cause more than 40 different neurological disorders. Although, traditionally, the position of the repeat within or outside of an open reading frame has been used to focus research on disease mechanisms involving protein loss of function, protein gain of function, or RNA gain of function, the discoveries of bidirectional transcription and repeat-associated non-ATG (RAN) have blurred these distinctions. Here we review what is known about RAN proteins in disease, the mechanisms by which they are produced, and the novel therapeutic opportunities they provide.
微卫星突变涉及三核苷酸、四核苷酸、五核苷酸或六核苷酸重复序列的扩展，可导致 40 多种不同的神经疾病。尽管传统上，重复序列在开放阅读框内或外的位置被用于将研究重点集中在涉及蛋白质功能丧失、蛋白质功能获得或 RNA 功能获得的疾病机制上，但双向转录和重复相关非 ATG（RAN）的发现模糊了这些区别。在这里，我们回顾了疾病中 RAN 蛋白的已知信息、它们产生的机制以及它们提供的新治疗机会。
