RAPID: Exosomal tRNA fragments may constitute an innate viral defense against SARS-CoV-2 and other respiratory RNA viruses.

RAPID：外泌体 tRNA 片段可能构成针对 SARS-CoV-2 和其他呼吸道 RNA 病毒的先天病毒防御。

• 批准号: 2030080
• 负责人: Glen Borchert
• 金额: $ 19.98万
• 依托单位: University of South Alabama
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-15 至 2022-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2030080&HistoricalAwards=false
• 关键词: RAPID; Exosomal; tRNA; fragments; may

Viral infection can induce formation of specific transfer RNA fragments (tRFs) that are packaged and released from host cells in exosomes. The project aims to discover the biological role of exosomal tRFs, specifically investigating whether uptake of these tRFs into uninfected cells triggers an innate antiviral immune response against SARS-CoV-2 and other respiratory RNA viruses. New insights into the influence of tRFs on host defense mechanisms against viral infections could be exploited to combat COVID-19 and future outbreaks of related viruses. The project also offers training opportunities for graduate and undergraduate students, the latter through bioinformatics course-based research.The project is based on preliminary data suggesting that tRF exosomal delivery constitutes a novel mechanism of innate antiviral immunity whereby tRFs prime host cells for a more robust interferon response. The research on SARS-CoV-2 will be guided by specific questions, for example, about the extent of exosomal tRF uptake and bioavailability in recipient cells, whether the tRFs hybridize with viral RNAs and activate interferon production through association with RIG-I, and whether intracellular tRFs inhibit viral replication in cells. Characterization of a novel host defense mechanism could potentially inform strategies for therapeutic intervention against COVID-19. This RAPID award is jointly funded by the Genetic Mechanisms Program in the Division of Molecular and Cellular Biosciences and the Established Program to Stimulate Competitive Research (EPSCoR), using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act.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.

病毒感染可以诱导特异性转移RNA片段（tRF）的形成，所述特异性转移RNA片段（tRF）在外泌体中被包装并从宿主细胞释放。该项目旨在发现外泌体tRFs的生物学作用，特别是研究这些tRFs是否被未感染的细胞吸收，从而引发针对SARS-CoV-2和其他呼吸道RNA病毒的先天性抗病毒免疫反应。关于tRFs对宿主抵抗病毒感染的防御机制的影响的新见解可以用于对抗COVID-19和未来相关病毒的爆发。该项目还为研究生和本科生提供培训机会，后者通过生物信息学课程为基础的研究。该项目是基于初步数据表明，tRF外泌体的交付构成了一种新的先天性抗病毒免疫机制，其中tRF总理宿主细胞更强大的干扰素反应。对SARS-CoV-2的研究将以具体问题为指导，例如，关于受体细胞中外泌体tRF摄取和生物利用度的程度，tRF是否与病毒RNA杂交并通过与RIG-I的结合激活干扰素的产生，以及细胞内tRF是否抑制细胞中的病毒复制。一种新型宿主防御机制的表征可能为COVID-19的治疗干预策略提供信息。该RAPID奖由分子和细胞生物科学部的遗传机制计划和刺激竞争性研究的既定计划（EPSCoR）共同资助，使用冠状病毒援助，救济和经济安全（CARES）法案的资金。该奖项反映了NSF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。

项目成果

SURFR: A Real-Time Platform for Non-Coding RNA Fragmentation Analysis Using Wavelets

SURFR：使用小波进行非编码 RNA 片段分析的实时平台

• DOI: 10.1109/bibm52615.2021.9669696
• 发表时间: 2021
• 期刊: 2021 IEEE International Conference on Bioinformatics and Biomedicine (BIBM
• 作者: Kasukurthi, Mohan Vamsi;Houserova, Dominika;Huang, Yulong;Li, Shengyu;Li, Dongqi;Lin, Jingwei;Yang, Guanhuan;Tan, Shaobo;Bourrie, David;Ma, Bin
• 通讯作者: Ma, Bin