Dual DNA/RNA-binding factor regulates dynamics of hnRNP splicing condensates
Ray, M.; Zaborowsky, J.; Mahableshwarkar, P.; Vaidyanathan, S.; Shum, J.; Viswanathan, R.; Huang, A.; Wang, S.-H.; Johnson, V.; Wake, N.; Conard, A. M.; Conicella, A. E.; Puterbaugh, R.; Fawzi, N. L.; Larschan, E.
Show abstract
How RNA splicing events are targeted to the correct genomic locations in specific cellular contexts to generate context-specific transcript diversity and prevent deleterious cryptic splicing remains very poorly understood. We show that a functionally conserved GA-rich DNA-binding transcription factor (TF), CLAMP, targets distinct RNA molecules in male and female cells to precisely regulate sex-specific splicing events through physical and functional interactions with RNA and RNA-binding proteins (RBPs). The prion-like domain of CLAMP (PrLD) and a stem-loop region in the target RNA are important for CLAMP-RNA interaction. Moreover, the CLAMP PrLD domain regulates sex-specific splicing by modulating the dynamics of an hnRNPA2/B1 family protein that regulates alternative splicing. Thus, we demonstrate that a TF targets co-transcriptional splicing to the correct genomic locations by directly linking DNA binding sites to RNA targets and modulating the dynamics of RBP partners that drive alternative splicing.
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