目前对于特定脑细胞和人类神经精神疾病中的环状RNA（circRNA）所知甚少。在这里，我们使用超深的总RNA测序，系统地鉴定了超过11,039个在190个人类脑和非神经元细胞中被激光捕获的易感多巴胺和金字塔形神经元中表达的circRNA。其中1526个和3308个circRNA特定于多巴胺和金字塔形神经元的细胞特性，并富集在突触途径中。29%的帕金森病相关基因和12%的阿尔茨海默病相关基因产生了经过验证的circRNA。从一种幼年发病帕金森病基因转录的circDNAJC6在常见帕金森病神经病理前期和起病阶段已经发生了异常调节。总体而言，与成瘾相关的基因主要在多巴胺神经元中产生circRNA，与自闭症相关的基因主要在金字塔形神经元中产生circRNA，而癌症则产生于非神经元细胞。本研究表明，人脑中的环状RNA适应于神经元的特性，并揭示了circRNA调控的突触专业化在神经精神疾病中的重要性。© 2023. Springer Nature Limited.

Little is known about circular RNAs (circRNAs) in specific brain cells and human neuropsychiatric disease. Here, we systematically identify over 11,039 circRNAs expressed in vulnerable dopamine and pyramidal neurons laser-captured from 190 human brains and non-neuronal cells using ultra-deep, total RNA sequencing. 1526 and 3308 circRNAs are custom-tailored to the cell identity of dopamine and pyramidal neurons and enriched in synapse pathways. 29% of Parkinson's and 12% of Alzheimer's disease-associated genes produced validated circRNAs. circDNAJC6, which is transcribed from a juvenile-onset Parkinson's gene, is already dysregulated during prodromal, onset stages of common Parkinson's disease neuropathology. Globally, addiction-associated genes preferentially produce circRNAs in dopamine neurons, autism-associated genes in pyramidal neurons, and cancers in non-neuronal cells. This study shows that circular RNAs in the human brain are tailored to neuron identity and implicate circRNA-regulated synaptic specialization in neuropsychiatric diseases.© 2023. Springer Nature Limited.