MicroRNA Regulation of Insect Diapause

了解昆虫滞育对于预测昆虫种群何时何地活跃和丰富至关重要。滞育是一种内部调节的休眠状态，允许昆虫在季节“逃脱”，例如冬季，当环境条件恶劣且不适合正常生长和活动时。滞育的特点是发育、代谢和环境抗逆性的变化。虽然已经有研究描述了滞育过程中发生的生理、生化和分子变化，但对滞育调控的认识还远远不够完整。本研究将通过研究小非编码RNA分子（microRNAs）如何调控滞育，为研究滞育的调控机制提供新的信息。这项研究将提高我们对这种适应不断变化的环境条件的重要理解。这项研究也有可能为管理医学和经济上重要的昆虫提供新的工具。例如，如果microRNA在昆虫滞育过程中的功能可以阻止或诱导昆虫在一年中的某个时间进入滞育，这将不利于昆虫的持续生存。这项研究有可能为癌症和糖尿病等人类医学疾病提供新的治疗方法，这些疾病在人类和昆虫中具有共同的微rna相关调节机制。最后，该项目还将为多名本科生提供综合培训和指导机会，同时还将通过对在校儿童和家庭的非正式科学教育向公众广泛传播研究结果。研究昆虫滞育为理解昆虫和其他动物如何感知环境线索并将其转化为表型变化提供了一个概念框架，使它们能够在遇到的生物和非生物挑战中生存。MicroRNAs （miRNAs，约22个核苷酸，非编码rna）是进化上保守的调控分子，在进化多样的物种中与滞育相关的生物过程（如发育停滞、代谢抑制和应激抵抗）中发挥重要作用。在肉蝇（Sarcophaga bullata）的蛹滞育过程中，有许多mirna受到调控，但它们的功能相关性目前尚不清楚。本项目的目的是利用计算和生化方法鉴定并实验验证滞育相关mirna的mRNA靶点。具体来说，该项目侧重于miRNA:mRNA对可能在环境抗性中发挥作用，这是滞育表型的一个决定性特征。它还研究了miRNA:mRNA调控网络的进化背景及其对多种昆虫滞育表型的贡献。总之，这项研究的结果有望为昆虫滞育的理解提供一个全新的维度，并为昆虫类中miRNA:mRNA相互作用的进化保护提供见解。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Understanding insect diapause is essential for predicting when and where insect populations will be active and abundant. Diapause is an internally regulated dormant state that allows insects to "escape" during seasons, such as winter, when the environmental conditions are harsh and unsuitable or normal growth and activity. Diapause is characterized by changes in development, metabolism, and environmental stress resistance. Although there have been studies that characterized physiological, biochemical, and molecular changes that occur during diapause, the understanding of diapause regulation is far from being complete. This research will provide new information about how diapause is regulated by investigating how small noncoding RNA molecules (microRNAs), regulate diapause. This study will improve our understanding of this important adaptation to changing environmental conditions. This research also has the potential to provide new tools for managing medically and economically important insects. For example, if microRNA function in insect diapause can block or induce diapause entry at a time of year that would be detrimental for their continued survival. This research has the potential to provide novel therapies for human medical disorders, such as cancer and diabetes, which share common, microRNA-associated regulatory mechanisms in humans and insects. Finally, the project will also provide integrative training and mentoring opportunities for multiple undergraduate students, while also broadly disseminating the findings to the public via informal science education to school children and families.Studying insect diapause provides a conceptual frame work for understanding how insects, and other animals, perceive environmental cues and translate them into phenotypic changes that allow them to survive biotic and abiotic challenges they encounter. MicroRNAs (miRNAs, ~22 nucleotide, noncoding RNAs) are evolutionarily conserved, regulatory molecules that have important roles in diapause-relevant biological processes (e.g. developmental arrest, metabolic repression, and stress-resistance) in evolutionarily diverse species. Numerous miRNAs are deferentially regulated during pupal diapause in the flesh fly, Sarcophaga bullata, but their functional relevance is currently unknown. The aim of this project is to identify, and experimentally validate, mRNA targets of diapause-relevant miRNAs using computational and biochemical approaches. Specifically, the project focuses on miRNA:mRNA pairs that may have a role in environmental stress-resistance, a defining feature of the diapause phenotype. It also investigates the evolutionary context of miRNA:mRNA regulatory networks and their contribution to the diapause phenotype in multiple insect species. Together, the results from the proposed research are expected to provide an entirely new dimension to the understanding of insect diapause as well as insights concerning the evolutionary conservation of miRNA:mRNA interactions across Insecta.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.