Reyes Charles Jourdan F, Asano Katsura
Institute of Neurogenetics, University of Lübeck.
Molecular Cellular and Developmental Biology Program, Division of Biology, Kansas State University.
Biol Pharm Bull. 2023;46(2):139-146. doi: 10.1248/bpb.b22-00448.
Repeat-associated non-AUG (RAN) translation is a pathogenic mechanism in which repetitive sequences are translated into aggregation-prone proteins from multiple reading frames, even without a canonical AUG start codon. Since its discovery in spinocerebellar ataxia type 8 (SCA8) and myotonic dystrophy type 1 (DM1), RAN translation is now known to occur in the context of 12 disease-linked repeat expansions. This review discusses recent advances in understanding the regulatory mechanisms controlling RAN translation and its contribution to the pathophysiology of repeat expansion diseases. We discuss the key findings in the context of Fragile X Tremor Ataxia Syndrome (FXTAS), a neurodegenerative disorder caused by a CGG repeat expansion in the 5' untranslated region of FMR1.
重复相关的非AUG（RAN）翻译是一种致病机制，即重复序列即使没有典型的AUG起始密码子，也能从多个阅读框被翻译成易于聚集的蛋白质。自从在8型脊髓小脑共济失调（SCA8）和1型强直性肌营养不良（DM1）中被发现以来，现在已知RAN翻译发生在12种与疾病相关的重复序列扩增的背景下。本文综述了在理解控制RAN翻译及其对重复序列扩增疾病病理生理学贡献的调控机制方面的最新进展。我们在脆性X震颤共济失调综合征（FXTAS）的背景下讨论了关键发现，FXTAS是一种由FMR1基因5'非翻译区的CGG重复序列扩增引起的神经退行性疾病。
