The nervous system is composed of highly polarized cells of complex and dynamic architecture. The formation and maintenance of neurons and neural circuits require the coordinated expression of genes at each step of RNA metabolism: from transcription, processing, localized transport and translation, to degradation. To achieve this level of complexity, neurons employ mechanisms that increase RNA regulatory potential: alternative splicing, alternative polyadenylation, and non-coding RNA expression.
One particularly striking process is the drastic lengthening of the 3’ untranslated region (3’ UTR) of hundreds of genes, which occurs in neurons from flies to humans. The function of the resulting ultra-long 3’ UTRs is unknown. RNA deregulation plays a central role in neurological diseases, which constitute a growing health concern in ageing populations; to understand underlying causes, it is essential to study regulatory processes and define the function of these RNA sequences. In this study, we integrate the molecular processes governing biogenesis and function of neuronal RNAs, from nucleus to synapse, in an animal model, the fruit fly Drosophila melanogaster.
Conclusions of the action: we found molecular mechanisms that govern the biogenesis of neuron-specific RNA signatures, and more generally, of gene expression regulation. We uncovered how ultra-long 3’UTRs are post-transcriptionally regulated, and the important contribution of highly conserved neuronal RNA-binding proteins in the processes of mRNA stability, localisation, and translation. One important aspect of our research is the demonstration of crucial functions carried out by neuronal 3’UTRs, individually and globally, during neurogenesis and in adult neuron physiology.
Overall, the results of this research made a major impact on our understanding of neuronal gene regulation in health and disease.
