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

摄食行为是一种具有高度可塑性的复杂表型。营养环境的变化影响食物搜寻行为、食物消耗和代谢表型。因此，调节摄食行为和新陈代谢的基因往往是可塑性调节的。此外，调节行为表型的基因往往是多效性的，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，即觅食基因。我证明了在转录水平上，不同的for基因产物的表达受到for启动子的遗传变异和表观遗传修饰的影响。除了转录调控外，转录后调控因子在调控基因表达方面也发挥着重要作用。在塑料表达基因的具体背景下，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，关于调控可塑性和多效性行为功能基因表达的转录后机制所知甚少。我的长期研究计划侧重于理解摄食行为和食物相关表型背后的转录和转录后调节过程。为了实现这一目标，本提案的重点是研究两种转录后基因调控机制，这两种机制在摄食行为的背景下尚未被研究。这包括rna结合蛋白的转录后调控（目标1）和mRNA表观遗传修饰的转录后调控（表转录组标记，目标2和3）。虽然已知mrna结合蛋白调节基因表达，但其在行为方面的功能尚不清楚。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。这一建议提出了第一步，以了解是否表观遗传景观mRNA行使类似的功能。本研究的两个机制目的是研究port-transcriptional regulation在众所周知的食物相关表型调节剂（for基因）表达中的作用：Aim1 -确定Pumilio在调节基因表达、摄食行为和代谢中的作用；Aim2 -确定表转录组标记m6A在调节基因表达、摄食行为和代谢中的作用。本提案的最后一个目标旨在为通过外转录组调控影响摄食行为的其他基因和途径建立广泛的基础：目标3 -鉴定通过外转录组调控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.