Choi Eun-Jin, Wu Wenzhe, Zhang Ke, Lee Inhan, Kim In-Hoo, Lee Yong Sun, Bao Xiaoyong
Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX, United States.
Department of Chemistry, The University of Houston Clear Lake, Clear Lake, TX, United States.
Front Mol Biosci. 2021 Feb 2;7:609732. doi: 10.3389/fmolb.2020.609732. eCollection 2020.
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in young children. However, effective treatment against RSV is unavailable. tRNA-derived RNA fragments (tRFs) are a recently discovered family of non-coding RNAs. We made an early observation that RSV infection causes significant induction of tRFs, which are mainly derived from the 5'-end of mature tRNAs (tRF5). However, their functions and biogenesis mechanism are not fully understood. Herein, we identified an enzyme responsible for the induction of a functional tRF5 derived from tRNA-Gln-CTG (tRF5-GlnCTG). We found that tRF5-GlnCTG promotes RSV replication and its induction, assessed by Northern blot and a new qRT-PCR-based method, is regulated by ribonuclease ELAC2. ELAC2-mediated tRF5 induction has never been reported. We also found that ELAC2 is associated with RSV N and NS1 proteins. Given the fact that tRF5-GlnCTG plays a role in RSV replication, the identification of ELAC2 being responsible for tRF5-GlnCTG induction could provide new insights into therapeutic strategy development against RSV infection.
呼吸道合胞病毒（RSV）是幼儿下呼吸道感染最常见的病因。然而，目前尚无针对RSV的有效治疗方法。tRNA衍生的RNA片段（tRFs）是最近发现的一类非编码RNA。我们早期观察到RSV感染会显著诱导tRFs，其主要来源于成熟tRNA的5'端（tRF5）。然而，它们的功能和生物发生机制尚未完全明确。在此，我们鉴定出一种负责诱导来源于tRNA-Gln-CTG的功能性tRF5（tRF5-GlnCTG）的酶。我们发现tRF5-GlnCTG促进RSV复制，并且通过Northern印迹法和一种基于qRT-PCR的新方法评估发现，其诱导受核糖核酸酶ELAC2调控。ELAC2介导的tRF5诱导此前从未被报道过。我们还发现ELAC2与RSV的N蛋白和NS1蛋白相关。鉴于tRF5-GlnCTG在RSV复制中发挥作用，鉴定出负责tRF5-GlnCTG诱导的ELAC2可为开发针对RSV感染的治疗策略提供新的见解。
