Investigating the Role of the hnRNP Glorund in the Drosophila Central Nervous System

Abstract

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are the most abundant RNA-binding proteins and are involved in every aspect of post-transcriptional gene regulation. In mammalian neuronal cells, the hnRNP F/H family is necessary for proper localization and translation of mRNA within axons, as well as axonal growth. Dysfunctions in human hnRNP F/H proteins have been linked to various neurodegenerative and neurodevelopmental disorders such as Parkinson’s disease and autism. Glorund (Glo) is the sole member of the hnRNP F/H family in Drosophila. Glo functions in several RNA regulatory steps during oogenesis, including alternative splicing and translational repression. During embryonic development, glo mRNA and protein become highly expressed in the central nervous system (CNS) of Drosophila. However, the role of Glo in the CNS has yet to be elucidated. Since Glo is highly expressed in the CNS, it may be involved in CNS development and the regulation of multiple CNS RNAs. Embryonic CNS morphology was analyzed in homozygous glo mutant embryos to determine if Glo plays a role in CNS development. Additionally, RNA co-immunoprecipitation experiments were performed and the HyperTRIBE method was attempted to search for in vivo targets of Glo. Although I was unable to fully complete the experiments, RNA co-immunoprecipitation results suggest Glo binds to IGF-II mRNA binding protein (imp) mRNA in stage 12–16 embryos. The work presented in this thesis has provided a foundation for several future experiments to probe Glo’s necessity in CNS development and for identification of multiple CNS targets of Glo, which will lead to a broader understanding of the multifunctionality of Glo and potentially the hnRNP F/H family as a whole.