The role of post-transcriptional regulation in feeding behaviour and metabolism

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Feeding behaviour is a complex phenotype with a high degree of plasticity. Changes in the nutritional environment affect food-search behaviour, food consumption, and metabolic phenotypes. Thus, genes that modulate feeding behaviour and metabolism are often plastically regulated. Furthermore, genes that regulate behavioural phenotypes are often pleiotropic, exercising multiple independent food-related functions through multiple gene products as well as time and tissue specific expression patterns. My previous research has focused on mapping the functions of one such plastic and pleiotropic gene, the foraging (for) gene. I showed that at the transcriptional level, expression of the different for gene products is affected by genetic variability in for's promoters and by epigenetic modifications. In addition to transcriptional regulation, post-transcriptional regulators can play an important role in regulating gene expression. In the context of plastically expressed genes specifically, post-transcriptional regulators might be crucial as they allow gene expression to change on short timescales. However, very little is known about the role post-transcriptional mechanisms play in regulating the expression of genes with plastic and pleiotropic behavioural functions. My long-term research program focuses on understanding the transcriptional and post-transcriptional regulatory processes that underlie feeding behaviour and food-related phenotypes. Towards this goal, this proposal focuses on investigating two post-transcriptional gene regulatory mechanisms that have not been investigated in the context of feeding behaviour. This includes post-transcriptional regulation by RNA-binding proteins (aim 1), and post-transcriptional regulation by mRNA epigenetic modifications (epitranscriptomic marks; aim 2 and 3). Although mRNA-binding proteins are known to regulate gene expression, their function in the context of behaviour is not well understood. Furthermore, the epigenetic landscape on DNA is emerging as an exciting interconnected system that shapes the effects of environment on development and behaviour. This proposal presents the first steps towards understanding if the epigenetic landscape on mRNA exercises a similar function. This proposal approaches the above questions with two mechanistic aims investigating the role of port-transcriptional regulation in expression of a well-known modulator of food-related phenotypes, the for gene: Aim1 - Determine the role of Pumilio in regulating for gene expression, feeding behaviour and metabolism and Aim2 - Determine the role of the epitranscriptomic mark m6A in regulating for gene expression, feeding behaviour, and metabolism. The last aim of this proposal seeks to establish a broad foundation for additional genes and pathways that are epitranscriptomically regulated to affect feeding behaviour: Aim 3 - Identify genes and pathways which are epitranscriptomically modified to regulate feeding behaviour and metabolism.