Identifying the mRNA Targets of the RNA-binding Protein TIA-1 in Human Neurodevelopment

TIA-1 is an RNA binding protein that is implicated in neurodevelopment. I conducted RIP-seq on lysates from three in vitro stages of neurodevelopment: human embryonic stem cells (hESCs), neural progenitor cells (NPCs), and cortical neurons, to identify TIA-1 targets during neurodevelopment. Despite minimal changes in TIA-1 expression or localization, TIA-1 binding efficiency decreases over neurodevelopment. RIP-seq identified 2365 TIA-1 targets in ESCs, 846 NPC targets, and 330 neuronal targets. ESCs targets included genes associated with neurodevelopment and autism, which were not bound in neurons. I validated TIA-1 binding to two mRNA targets critical to neurodevelopment, UBE3A and MECP2, using RIP qRT-PCR. These results provide insight into the network of TIA-1 targets during neurodevelopment and provide a first step towards defining the functional role of TIA-1 in neuronal differentiation. They suggest that TIA-1 regulates neurodevelopmentally relevant transcripts in early stages of development, but that this regulation decreases during neuronal differentiation.M.Sc