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J Gen Virol. 2017 Jul;98(7):1600-1610. doi: 10.1099/jgv.0.000852. Epub 2017 Jul 15.

Identification of two novel functional tRNA-derived fragments induced in response to respiratory syncytial virus infection.

Zhou J1, Liu S1,2, Chen Y1,2, Fu Y1, Silver AJ1,3, Hill MS1, Lee I4, Lee YS5,6, Bao X7,8,1.

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Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.
Department of Pediatrics, TongJi Hospital, Huazhong University of Science and Technology, PR China.
Department of Chemistry, Williams College, Williamstown, MA, USA.
miRcore, Ann Arbor, MI, USA.
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
Department of Cancer System Science, Graduate School of Cancer Science and Policy, National Cancer Center, Republic of Korea.
Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
Institute for Translational Science, University of Texas Medical Branch, Galveston, Texas, TX, USA.


Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection (LRTI) in children from infancy up to early childhood. Recently, we demonstrated that RSV infection alters cellular small non-coding RNA (sncRNA) expression, most notably the tRNA-derived RNA fragments (tRFs). However, the functions of the tRFs in virus-host interaction are largely unknown. Herein, we examined the role of three RSV-induced tRFs derived from the 5-end of mature tRNAs decoding GlyCCC, LysCTT and CysGCA (named tRF5-GlyCCC, tRF5-LysCTT and tRF5-CysGCA, respectively) in controlling RSV replication. We found that tRF5-GlyCCC and tRF5-LysCTT, but not tRF5-CysGCA, promote RSV replication, demonstrating the functional specificity of tRFs. The associated molecular mechanisms underlying the functions of tRF5-GlyCCC and tRF5-LysCTT were also investigated. Regulating the expression and/or activity of these tRFs may provide new insights into preventive and therapeutic strategies for RSV infection. The study also accumulated data for future development of a tRF targeting algorithm.

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