Poster abstracts
Poster number 78 submitted by Seth Kelly
The evolutionarily conserved polyadenosine RNA binding protein Nab2 regulates mRNA splicing in the developing Drosophila melanogaster nervous system
Seth M. Kelly (Department of Biology and Program in Neuroscience The College of Wooster), Allison Paschack, Gargi Mishra, Katie Shelmidine (Program in Biochemistry and Molecular Biology, The College of Wooster), Jinsoo Ahn, Kichoon Lee (Department of Animal Sciences, The Ohio State University), Emma Smith (Department of Biology, The College of Wooster), Young Ji (Program in Neuroscience, The College of Wooster)
Abstract:
Due to the interconnected nature of mRNA processing events, mutations in the genes encoding RNA binding proteins can lead to pleiotropic disease phenotypes. Thus, understanding how RNA binding proteins individually and collectively post-transcriptionally regulate gene expression can provide a comprehensive understanding of RNA processing and underlying mechanisms of disease. For example, mutations in the vertebrate ZC3H14 gene, which encodes an evolutionarily conserved RNA binding protein, cause alterations in transcript abundance, extended poly(A) tails, and changes to alternative mRNA splicing. The yeast and Drosophila orthologs of ZC3H14, both called Nab2, have likewise been implicated in multiple aspects of RNA metabolism, including poly(A) tail length control, alternative splicing, and RNA methylation. Importantly, mutations in ZC3H14 and Nab2 are linked to changes in nervous system function and development, suggesting that these proteins are especially critical for RNA processing in neurons.
To better understand the network of interactions that ZC3H14 and Nab2 participate in, we investigated functional interactions between Drosophila Nab2 and RNA processing components. We show here that Nab2 genetically interacts with multiple components of the spliceosome, supporting a functional connection between Nab2 and mRNA processing. In support of this connection, we have also demonstrated that Nab2 is required for control of alternative splicing and prevention of intron retention during fly brain development. Finally, long-read RNA sequencing data suggests that during development, changes in splicing occur independent of changes in poly(A) tail length. Together, these data suggest that Nab2 may function as a regulator of alternative splicing during brain development. The alterations in RNA processing that we have observed may also contribute to the developmental and behavioral alterations observed in Nab2 null flies and ZC3H14 null mice.
Keywords: RNA Binding proteins , splicing, polyadenylation