The psychosis risk gene RBM12 encodes a novel repressor of GPCR/cAMP signal transduction

A deeper understanding of the regulation of G protein-coupled receptors (GPCRs) and their associated downstream cascades will provide critical insights into how these pathways shape human physiology and disease, and could yield novel therapeutic targets. Here, we validate and characterize RNA-binding motif 12 (Rbm12) as a repressor of GPCR/cAMP signaling. We established Rbm12 CRISPR KO HEK293 cells using two independent gRNAs and human iPSC-derived neurons (iNeuron) depleted of Rbm12 via CRISPR interference. Then, we performed basal gene expression profiling (HEK293) and basal + beta-2-adrenergic receptor induced (1 hour of 1 uM Isoproterenol) conditions (neurons). Overall design: Comparative gene expression profiling analysis of RNA-seq data for HEK293 cells (WT, RBM12 KO 1, RBM12 KO 2) and neurons (WT, RBM12 knockdown), treated with isoproterenol or untreated.