Characterization of variations responsible for neurodevelopmental disorders in the PTBP1 and PTBP2 genes

Heterogeneous nuclear ribonucleoproteins (hnRNPs) polypyrimidine tract-binding protein 1 and 2 (PTBP1 and PTBP2) are splicing regulators, shuttling between nucleus and cytoplasm thanks to the action of partially overlapping nuclear localization and export signals (NLS and NES respectively). These two paralog proteins share similar RNA binding properties although they exhibit different expression levels and kinetics, post-translational modifications and cofactor interactions across tissues and cell types, thus regulating RNA metabolism in a cell- specific manner. Despite their fundamental role as alternative splicing factors implicated in cell growth, neuronal cell differentiation, and immun…