Role of cellular and vesicular microRNAs in the transcriptomic regulation of the nervous system.
Supervisor: Alexandre Favereaux – IINS – Team: Central Mechanisms of Pain Sensitization
Abstract
This work consists in stuying the expression, the role and the transport of microRNAs (miRNAs) in the central nervous system (CNS). microRNAs (miRNAs) are small endogenous non coding RNAs, exerting a negative regulation on gene expression.They inhibit protein translation by hybridization on the 3’ untranslated region of mRNA.First, we have revealed the specific role of miR-92a in the control of the expressionof GluA1, in an homeostatic plasticity paradigm in which the synaptic plasticity is inhibited.Second, by using RNA-Seq technology, we showed that miRNAs are differentially expressed in the different structures of the CNS. Moreover, we have discovered new species of miRNAs. Finally, our results suggest that the miRNA expression (of known and new miRNAs) participate in the singular transcriptomique signature of each structure.Third, we have shown that miRNAs are transported into EVs, and can be exchanged between the cells of the CNS. The miRNA content of EVs varies depending on neuronal activity. Target prediction of these miRNAs includes genes involved in the regulation of neuronal plasticity. Together, our results suggest that the exchange of miRNAs through EVs is a new mechanism involved in the modulation of neuronal plasticity. Finally, we propose a new tool for purifiying EVs depending on their cellular origin.To conclude, this study allows a better understanding of the role of miRNAs in the regulation of the physiology of the CNS.