Role of Circular RNAs in Innate Immunity and Neuro-development

项目总结 拟议研究的目标是识别和确定环状RNA的功能 (CircRNAs)在先天免疫和神经发育中。适当地激活免疫 反应对寄主的健康至关重要。同时有效地控制入侵病原体或对 内源性应激信号依赖于免疫信号通路的快速而有力的诱导， 长期的或异常的激活，无论是系统的还是局部的，都可能导致病理情况 例如自身免疫、癌症和神经退行性变。尤其是大脑中的慢性炎症 与神经发育和功能受损有关。因此，无论是规模还是持续时间 免疫反应需要受到严格的监管。非编码RNA(NcRNAs)在 在多种生物体中调节抗病毒免疫。深度测序技术的最新进展 技术和计算生物学极大地扩展了调控ncRNA的谱系， 而CircRNAs是最新增加的。除了它们独特的构型外，CircRNA还与 他们的典型的线性兄弟姐妹通过窝藏频繁的外显子扰乱事件。最初被视为 仅仅是罕见的“头到尾”反向剪接事件的副产品，CircRNAs最近 以真核生物中丰富的一类RNA为特征的。但是，除了只有 在少数CircRNA中，绝大多数的功能尚不清楚。我们确定了一组 在果蝇中对细菌感染有差异表达的CircRNAs，以及我们的 初步研究表明，富含脑部的CircRNA Edis与先天免疫和神经功能有关。 发展。我们假设EDIS调节先天免疫信号和神经发育。 和功能，并建议采用基因组、计算、遗传和 利用生物化学方法确定EDIS的功能并阐明其调控机制 基础EDIS表达式。 拟议研究的完成将使CircRNAs成为一类新的监管ncRNAs， 阐明CircRNA表达的调控机制，并确定其在调控中的作用 先天免疫和神经发育。这将促进我们对它们在进化上的理解 ，并提供了对潜在机制的新见解。 在生理和病理环境中，先天免疫和神经发育之间的相互作用。

PROJECT SUMMARY The goal of the proposed study is to identify and determine the function of circular RNAs (circRNAs) in innate immunity and neuro-development. Appropriate activation of the immune response is crucial for host fitness. While effective control of invading pathogens or response to endogenous stress signals depend on rapid and robust induction of immunity signaling pathways, prolonged or aberrant activation, either systemically or locally, can lead to pathological conditions such as autoimmunity, cancer and neurodegeneration. In particular, chronic inflammation in the brain is associated with impaired neuro-development and function. Thus both the magnitude and duration of the immune response need to be tightly regulated. Non-coding RNAs (ncRNAs) play a critical role in modulating antiviral immunity in a wide variety of organisms. Recent advances in deep-sequencing technology and computational biology have greatly expanded the repertoire of regulatory ncRNAs, and circRNAs are the latest addition. Besides their unique configurations, circRNAs are distinct from their canonical linear siblings by harboring frequent exon scrambling events. Originally viewed as merely by-products of rare “head-to-tail” back-splicing events, circRNAs have recently been characterized as an abundant class of RNAs in eukaryotes. However, with the exception of only a handful of circRNAs, the function of the vast majority is unknown. We identified a collection of circRNAs in Drosophila that are differentially expressed in response to bacterial infection, and our preliminary studies have implicated the brain-enriched circRNA Edis in innate immunity and neuro- development. We hypothesize that Edis modulates innate immunity signaling and neuro-development and function, and propose to employ a combination of genomic, computational, genetic, and biochemical approaches to establish the function of Edis and elucidate the regulatory mechanism underlying Edis expression. Completion of the proposed study will establish circRNAs as a new class of regulatory ncRNAs, elucidate the regulatory mechanism of circRNA expression, and determine their function in modulating innate immunity and neuro-development. This will advance our understanding of their evolutionarily conserved mammalian counterparts, and provide new insights into the mechanisms underlying the interplay between innate immunity and neuro-development in physiological and pathological settings.