From development to disease: the neuronal role of hnRNPs through the lens of Drosophila

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a large family of RNA-binding proteins (RBPs) involved in multiple aspects of nucleic acid metabolism, ranging from DNA maintenance to RNA splicing and translation. As a consequence, hnRNPs play a pivotal role during development and in cellular homeostasis, and their dysregulation has been linked to a wide range of diseases, in particular cancer and neurodegenerative disorders. Owing to the high evolutionary conservation of their domains and functions, the fruit fly Drosophila melanogaster represents a useful model for the study and characterisation of different families of RBPs. To date, 14 hnRNPs homologous to mammalian proteins have been identified in fruit flies. Here, we review the main Drosophila hnRNPs and their parallels with mammalian counterparts, focusing on their functional roles in neuronal development and neurophysiological processes and, in particular, neurodegenerative diseases. Importantly, we discuss the current use of Drosophila models in the study of hnRNP-related neurodegenerative conditions and highlight the still largely unexplored potential of this organism in unveiling their underlying molecular mechanisms.