Center for Neuro-Genetics, University of Florida, Gainesville, Florida 32610.
Departments of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida 32610.
Cold Spring Harb Perspect Biol. 2018 Dec 3;10(12):a033019. doi: 10.1101/cshperspect.a033019.
More than 40 different neurological diseases are caused by microsatellite repeat expansions that locate within translated or untranslated gene regions, including 5' and 3' untranslated regions (UTRs), introns, and protein-coding regions. Expansion mutations are transcribed bidirectionally and have been shown to give rise to proteins, which are synthesized from three reading frames in the absence of an AUG initiation codon through a novel process called repeat-associated non-ATG (RAN) translation. RAN proteins, which were first described in spinocerebellar ataxia type 8 (SCA8) and myotonic dystrophy type 1 (DM1), have now been reported in a growing list of microsatellite expansion diseases. This article reviews what is currently known about RAN proteins in microsatellite expansion diseases and experiments that provide clues on how RAN translation is regulated.
超过 40 种不同的神经疾病是由位于翻译或非翻译基因区域内的微卫星重复扩展引起的，包括 5'和 3'非翻译区 (UTR)、内含子和编码蛋白的区域。扩展突变是双向转录的，并已被证明会产生蛋白质，这些蛋白质是通过一种称为重复相关非 AUG（RAN）翻译的新过程从三个阅读框中合成的，而没有 AUG 起始密码子。RAN 蛋白最初在脊髓小脑共济失调 8 型 (SCA8) 和肌强直性营养不良 1 型 (DM1) 中被描述，现在已经在不断增加的微卫星扩展疾病列表中被报道。本文综述了目前已知的微卫星扩展疾病中 RAN 蛋白的情况，以及为阐明 RAN 翻译如何受到调控而进行的实验。
