Dong Xianjun, Bai Yunfei, Liao Zhixiang, Gritsch David, Liu Xiaoli, Wang Tao, Borges-Monroy Rebeca, Ehrlich Alyssa, Serano Geidy E, Feany Mel B, Beach Thomas G, Scherzer Clemens R
APDA Center for Advanced Parkinson Disease Research, Harvard Medical School, Brigham & Women's Hospital, Boston, MA, USA.
Precision Neurology Program, Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
bioRxiv. 2023 Apr 3:2023.04.01.535194. doi: 10.1101/2023.04.01.535194.
Little is known about circular RNAs (circRNAs) in specific brain cells and human neuropsychiatric disease. Here, we systematically identified 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. 1,526 and 3,308 circRNAs were custom-tailored to the cell identity of dopamine and pyramidal neurons and enriched in synapse pathways. 88% of Parkinson's and 80% of Alzheimer's disease-associated genes produced circRNAs. produced from a juvenile-onset Parkinson's gene, was already dysregulated during prodromal, onset stages of common Parkinson's disease neuropathology. Globally, addiction-associated genes preferentially produced 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.
关于特定脑细胞和人类神经精神疾病中的环状RNA（circRNA），我们了解甚少。在此，我们通过超深度全RNA测序，系统地鉴定了从190个人类大脑中激光捕获的脆弱多巴胺能神经元和锥体神经元以及非神经元细胞中表达的超过11,039种circRNA。1,526种和3,308种circRNA是根据多巴胺能神经元和锥体神经元的细胞特性定制的，并在突触途径中富集。88%的帕金森病相关基因和80%的阿尔茨海默病相关基因产生circRNA。由青少年型帕金森病基因产生的 ，在常见帕金森病神经病理学的前驱期和发病期就已经失调。总体而言，成瘾相关基因在多巴胺能神经元中优先产生circRNA，自闭症相关基因在锥体神经元中优先产生circRNA，癌症相关基因在非神经元细胞中优先产生circRNA。这项研究表明，人类大脑中的环状RNA是根据神经元特性定制的，并暗示circRNA调节的突触特化与神经精神疾病有关。
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