Yabuki Yasushi, Shioda Norifumi
Department of Genomic Neurology, Institute of Molecular Embryology and Genetics, Kumamoto University.
Nihon Yakurigaku Zasshi. 2023;158(1):30-33. doi: 10.1254/fpj.22078.
Repeat expansion diseases are caused by the aberrant repeat expansions within specific genes. RNAs derived from aberrant repeat sequences form non-canonical secondary structures, contributing to induce cell toxicity. In particular, RNA G-quadruplexes (G4RNAs) formed in guanine-rich repeat expanded RNAs trigger neurodegeneration. We have previously shown that the expanded CGG repeat-derived G4RNAs initiate aggregation of FMRpolyG, a neuropathogenic protein generated by repeat-associated non-AUG (RAN) translation in Fragile X-associated tremor/ataxia syndrome (FXTAS). In this review, we describe the neuropathological mechanism attributed to G4RNAs in guanine-rich repeat expansion diseases, including FXTAS.
重复序列扩张疾病是由特定基因内异常的重复序列扩张引起的。源自异常重复序列的RNA形成非典型二级结构，从而导致细胞毒性。特别是，富含鸟嘌呤的重复序列扩张RNA中形成的RNA G-四链体（G4RNAs）引发神经退行性变。我们之前已经表明，扩展的CGG重复序列衍生的G4RNAs引发了FMRpolyG的聚集，FMRpolyG是一种在脆性X相关震颤/共济失调综合征（FXTAS）中由重复相关非AUG（RAN）翻译产生的神经致病蛋白。在这篇综述中，我们描述了富含鸟嘌呤的重复序列扩张疾病（包括FXTAS）中G4RNAs的神经病理机制。
