Regulation of pre-mRNA splicing plays a significant role in neurons by diversifying the proteome and modulating gene expression during development and in response to physiological cues. Although most pre-mRNA processing reactions are thought to occur in the nucleus, numerous RNA splicing regulators are also found in neurites, however, very little is known about their extra-nuclear functions. We have recently shown that the non-nuclear pool of a major spliceosome component (SNRNP70) modulates the production of alternative spliced mRNA isoforms essential for motor connectivity and protects transcripts from degradation.

This project aims to investigate the extra-nuclear activities of SNRNP70 in the context of neuronal connectivity in zebrafish. The ease of genetic manipulations together with the translucency and small size of their offspring allows us to monitor neural cell behaviour and function and observe changes in neuronal connectivity. We will use a range of genetic tools, including transgenic over-expression of cytoplasmic SNRNP70 and nuclear-only SNRNP70 zebrafish knock-in lines to establish developmental functions attributed to the cytoplasmic pool of SNRNP70. The results from this project will contribute to our understanding of how local RNA metabolism in axons contributes to the normal development of neural connections in the brain.