Respiratory Syncytial Virus Utilizes a tRNA Fragment to Suppress Antiviral Responses Through a Novel Targeting Mechanism

作者：Junfang Deng, Ryan Ptashkin, Yu Chen, Cheng Zhi, Guangliang Liu, T. Phan, Xiaoling Deng, Jiehua Zhou, Inhan Lee, Yong Sun Lee, Xiaoyong Bao · 发表于：Molecular Therapy · 年份：2015 · DOI：10.1038/mt.2015.124 · 被引用次数：186 · 研究领域：RNA modifications and cancer、Cancer-related molecular mechanisms research、Respiratory viral infections research

Target identification is highly instructive in defining the biological roles of microRNAs. However, little is known about other small noncoding RNAs; for example, tRNA-derived RNA Fragments (tRFs). Some tRFs exhibit a gene-silencing mechanism distinctly different from that of typical microRNAs. We recently demonstrated that a respiratory syncytial virus (RSV)-induced tRF, called tRF5-GluCTC, promotes RSV replication. RSV is the single most important cause of lower respiratory tract infection in children. By using biochemical screening and bioinformatics analyses, we have identified apolipoprotein E receptor 2 (APOER2) as a target of tRF5-GluCTC. The 3'-portion of tRF5-GluCTC recognizes a target site in the 3'-untranslated region of APOER2 and suppresses its expression. We have also discovered that APOER2 is an anti-RSV protein whose suppression by tRF5-GluCTC promotes RSV replication. Our report represents the first identification of a natural target of a tRF and illustrates how a virus utilizes a host tRF to control a host gene to favor its replication.