Abstract
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. circDNAJC6, 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.
Competing Interest Statement
Brigham and Women's Hospital holds US provisional patent applications on biomarkers for PD, on which C.R.S. is named as inventor or co-inventor. Outside this work, C.R.S. has served as consultant, scientific collaborator or on scientific advisory boards for Sanofi, Berg Health, Pfizer, Biogen, and has received grants from NIH, U.S. Department of Defense, APDA, ASAP, and MJFF. X.D. has received funding from NIH, APDA, and ASAP. The other authors declare no competing financial interests.
