环形RNA与天然免疫调控机制及潜在应用

批准号:
32000912
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
刘楚霄
依托单位:
学科分类:
核酸生物化学
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
刘楚霄
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中文摘要
近年来国内外研究发现多种新型长非编码RNA分子家族及其全新生成机制和重要调控功能,其中,有一类来源于外显子反向剪接的环形RNA。环形RNA具有特殊双链结构、能够结合天然免疫因子核酸受体、在病毒感染下被快速降解等特征,前期工作发现环形RNA在天然免疫调控中扮演重要角色并与自身免疫性疾病系统性红斑狼疮密切关联,这些工作开辟了环形RNA功能研究的新方向和应用潜能。本项目拟发展新手段揭示环形RNA的生物学功能及其在天然免疫调控中的分子基础;揭示环形RNA所调控的天然免疫通路与自身免疫疾病如红斑狼疮的关联;创建高效体系合成具有结构、稳定的、无免疫源性的环形RNA,结合小鼠模型探索利用环形RNA开展治疗自身免疫疾病的可能。研究结果将为环形RNA在天然免疫中的重要功能奠定基础,并有望揭示这类具有特殊结构的RNA在自身免疫性疾病治疗中的潜在价值。
英文摘要
In recent years, researchers have identified various lncRNA species with new formats including broadly expressed circular RNAs (circRNAs). Importantly, some circular RNAs have been implicated in gene regulation and human diseases. Focusing on circRNAs, our previous work demonstrate that their expression is widespread and their biogenesis is promoted by flanking intronic complementary sequences and trans-factors such as dsRNA-binding immune-factors NF90/NF110. Recently, we show that circRNAs tend to form 16-26 bp intra-molecularly double-stranded (ds) RNAs (intra-dsRNAs) and are inhibitors of dsRNA-activated protein kinase (PKR) related to innate immunity. Upon viral infection, circRNAs are globally degraded by RNase L, a process required for PKR activation in early cellular innate immune responses. Importantly, augmented PKR phosphorylation and circRNA reduction are found in peripheral blood mononuclear cells (PBMCs) derived from patients of autoimmune disease systemic lupus erythematosus (SLE). Over-expression of circRNA in PBMCs or T cells derived from SLE can alleviate the aberrant PKR activation cascade, thus providing a connection between circRNAs and SLE. Collectively, by addressing circRNA biogenesis, structure and degradation, we have uncovered their important roles in innate immunity regulation and the exciting potential of modulating circular RNA levels as a therapeutic strategy for SLE. In a word, this research proposal will dissect the molecular basis of circular RNA in innate immunity regulation and explore the potential application of circular RNAs as a therapeutic strategy for autoimmune diseases.
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科研奖励列表
会议论文列表
专利列表
环形RNA在银屑病(psoriasis)干预治疗中的分子机制及潜在应用
- 批准号:32371349
- 项目类别:面上项目
- 资助金额:50万元
- 批准年份:2023
- 负责人:刘楚霄
- 依托单位:
国内基金
海外基金
