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

摄食行为是一个具有高度可塑性的复杂表型。营养环境的变化影响食物搜索行为，食物消费和代谢表型。因此，调节摄食行为和代谢的基因通常是可塑性调节的。此外，调节行为表型的基因通常是多效性的，通过多种基因产物以及时间和组织特异性表达模式行使多种独立的食物相关功能。我以前的研究集中在绘制这样一个可塑性和多效性基因的功能，觅食基因。我证明了在转录水平上，不同for基因产物的表达受到for启动子的遗传变异性和表观遗传修饰的影响。除了转录调控外，转录后调控因子在基因表达调控中也发挥重要作用。特别是在可塑性表达基因的背景下，转录后调节因子可能是至关重要的，因为它们允许基因表达在短时间内发生变化。然而，很少有人知道的作用，转录后机制发挥调节基因的表达与塑料和多效性的行为功能。我的长期研究计划的重点是了解的转录和转录后调控过程，基础喂养行为和食物相关的表型。为了实现这一目标，本建议的重点是调查两个转录后基因调控机制，尚未调查的背景下，喂养行为。这包括通过RNA结合蛋白的转录后调节（目的1）和通过mRNA表观遗传修饰的转录后调节（表观转录组学标记;目的2和3）。虽然已知mRNA结合蛋白调节基因表达，但它们在行为背景下的功能还不清楚。此外，DNA上的表观遗传景观正在成为一个令人兴奋的相互关联的系统，它塑造了环境对发育和行为的影响。该提案提出了理解mRNA上的表观遗传景观是否行使类似功能的第一步。该建议以两个机制目的来解决上述问题，即研究端口转录调节在食物相关表型的众所周知的调节剂for基因表达中的作用：目的1-确定Pumilio在调节基因表达、摄食行为和代谢中的作用，目的2-确定表位转录组标记m6 A在调节基因表达、摄食行为、和新陈代谢。本提案的最后一个目的是寻求为表转录组学调节以影响摄食行为的其他基因和途径建立广泛的基础：目的3 -鉴定表转录组学修饰以调节摄食行为和代谢的基因和途径。

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.