RBM45 is an m6A-binding protein that affects neuronal differentiation and the splicing of a subset of pre-mRNAs IV

Here, we identify RNA-binding motif containing protein 45 (RBM45) as a novel m⁶A reader, enriched in the brain, and highly expressed during embryonic neurodevelopment. We demonstrate that RBM45 recognizes intronic m⁶A and that its primary role is as a direct regulator of pre-mRNA splicing for its target genes, many of which are associated with neurodevelopment. Furthermore, we show that RBM45 is absolutely required for proper differentiation in cultured SH-SY5Y neuroblastoma cells, and that RBM45 regulates splicing of neurodevelopmental target genes central to the activation of gene expression programs that regulate differentiation in vitro. in vitro DART-seq m⁶A profiling on subcellular fractionated RNAs (chromatin associated (CA), nuclear, and cytoplasmic RNA) from immortalized mouse hippocampal neurons (mHiPPoE-2)