Pathogenic mechanism and therapeutic intervention of impaired N7-methylguanosine (m7G) tRNA modification

Mutations of tRNA modification enzymes including the tRNA m7G methyltransferase complex component WDR4 were frequently found in patients with neural disorders, while the pathogenic mechanism and therapeutic intervention strategies are poorly explored. In this study, we revealed that patient-derived WDR4 mutation leads to temporal and cell-type-specific neural degeneration, and directly causes neural developmental disorders in mice. TRAC-Seq were used to identify the tRNA m7G methylome in mouse brain. RNC-seq was used to identified genes with different translation efficiency in mouse brain upon WDR4 mutation.RNA-seq was used to study the differential gene expression in the mice brain between Wdr4 point mutation and control mice. snRNA-seq were performed for the analysis of cellular components in brain.