Protein arginine methyltransferase 7 is linked to schizophrenia by regulating the function of neural progenitor cell

Schizophrenia (SCZ) is a severe mental disorder with strong heritability and complex inheritance, which affects about 1% of populations worldwide. In this study, we prioritized protein arginine methyltransferase 7 (PRMT7) for SCZ susceptibility. Next, we explored the cellular and molecular infrastructures conferring PRMT7 to SCZ risk. Down-regulation of PRMT7 in neural progenitor cells (NPCs) caused decreased proliferation and increased neuronal differentiation. Additionally, the differentiated neurons derived from these NPCs displayed longer neurites compared to controls. Conversely, Over-expression of PRMT7 led to enhanced NPC proliferation and reduced neuronal differentiation. Moreover, in 3D cerebral organoids, the similar NPC phenotypic changes were observed following PRMT7 depletion. Mechanistically, the expression of genes related to cell cycle and neuronal functions were under regulation of PRMT7 via depositing H4R3me2s on their promoter regions. Disease enrichment analysis revealed that these PRMT7-regulated genes were more strongly associated with SCZ compared to other mental disorders. In summary, this study uncovers that PRMT7 is a functional gene at 16q22.1 contributing to the etiology of SCZ by impacting the proliferation and differentiation of NPCs as an epigenetic regulator.