A new dimension to the olfactory system: long non-coding (lnc)RNAs and a lncRNA-encoded micropeptide

About This Grant

Olfaction plays a critical role in animal survival, enabling the detection of food sources, dangers, and potential mates. The remarkable plasticity of the olfactory system allows for the modification of responses to cues based on various internal states. However, the precise mechanisms underlying olfactory plasticity, particularly at the level of peripheral sensory neuronal activity, remain poorly understood. In this research proposal, we aim to investigate the role of long non-coding (lnc)RNA-micropeptide systems in the functions of olfactory receptor neurons. LncRNAs are transcripts longer than 500 nucleotides that lack an open reading frame longer than 100 codons. Various lncRNAs have been implicated in neural development, function, and diseases. While lncRNAs are traditionally considered non-coding, certain lncRNAs encode micropeptides, which can contribute to diverse biological processes. Despite their potential importance, the functions of lncRNA-micropeptide systems in the nervous system, particularly in olfaction, remain largely unexplored. To address this knowledge gap, we will capitalize on the well-characterized olfactory system of the fruit fly. This system offers several advantages, including numerical simplicity, well-defined neurons that drive complex behaviors, and the availability of powerful genetic tools. We recently generated a comprehensive survey of lncRNAs in the main fly olfactory organ that demonstrated the diversity and expression patterns of lncRNAs in the olfactory system and set the stage for investigating their functional roles and their impact on sensory behaviors. Through a multidisciplinary approach that includes genetic, electrophysiological, behavioral, and molecular assays, we will test the hypothesis that lncRNA-micropeptide systems contribute to olfactory function. Our initial focus will be on the lncRNA AnRUS (Antennal RNA Upregulated by Starvation) and its micropeptide. We have recently shown AnRUS is modulated by nutrient availability and food odor, and acts in the modulation of the response of a pheromone-sensing neuron to odors. Here, we will investigate the mechanism by which AnRUS modulates neuronal responses and how its expression is regulated by nutrients and food odors. Finally, we will expand our investigation by characterizing the micropeptidome of the antenna, a first step toward exploring the regulatory roles of these micropeptides in olfaction.