Deviations from the optimal level of mRNA translation are linked to disorders with high rates of autism. Loss of function mutations in genes encoding translational repressors such as PTEN, TSC1, TSC2, and FMRP are associated with autism spectrum disorders (ASDs) in humans and their deletion in animals recapitulates many ASD-like phenotypes. Importantly, the activity of key translational control signaling pathways such as PI3K-mTORC1 and ERK is frequently dysregulated in autistic patients and animal models and their normalization rescues many abnormal phenotypes, suggesting a causal relationship. Mutations in several genes encoding proteins not directly involved in translational control have also been shown to mediate ASD phenotypes via altered signaling upstream of translation. This raises the possibility that the dysregulation of translational control signaling is a converging mechanism not only in familiar but also in sporadic forms of autism. Here, we overview the current knowledge on translational signaling in ASD and highlight how correcting the activity of key pathways upstream of translation reverses distinct ASD-like phenotypes.

mRNA 翻译最佳水平的偏差与自闭症发病率高有关。编码翻译抑制因子（如 PTEN、TSC1、TSC2 和 FMRP）的基因功能丧失与人类自闭症谱系障碍 (ASD) 相关，并且它们在动物中的缺失重现了许多 ASD 样表型。重要的是，PI3K-mTORC1 和 ERK 等关键翻译控制信号通路的活性在自闭症患者和动物模型中经常失调，它们的正常化挽救了许多异常表型，表明存在因果关系。编码不直接参与翻译控制的蛋白质的几个基因的突变也已被证明通过改变翻译上游的信号传导来介导 ASD 表型。这提出了一种可能性，即翻译控制信号的失调是一种收敛机制，不仅在熟悉的自闭症中，而且在零星的自闭症形式中也是如此。在这里，我们概述了 ASD 中翻译信号传导的当前知识，并强调了纠正翻译上游关键途径的活动如何逆转不同的 ASD 样表型。