The Role of Cryptic Exon Repression in Neurogenesis and Neurodegeneration

Recent developments in next generation sequencing technology have rapidly advanced our understanding of the mammalian brain. With RNA sequencing technology (RNA-seq), it is now possible to generate quantifiable, genome-wide transcript expression data at the base-pair level of resolution. Such datasets have provided many insights into the molecular mechanisms that underlie both neurogenesis and neurodegenerative disease. Utilizing these techniques, we have recently identified novel functions for the RNA binding proteins TDP-43, PTBP1 and PTBP2. TDP-43 has been implicated in the pathogenesis of several diseases, including amyotrophic lateral sclerosis and frontotemporal dementia. In contrast, PTBP1 and PTBP2 have been identified as key regulators of neuronal differentiation. Our findings indicate that TDP-43, PTBP1 and PTBP2 belong to a family of splicing factors that share a common mechanism of action