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

Junfang Deng, Ryan N. Ptashkin, Yu Chen, Zhi Cheng, Guangliang Liu, Thien Phan, Xiaoling Deng, Jiehua Zhou, Inhan Lee, Yong Sun Lee, Xiaoyong Bao

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1622-1629
Number of pages8
JournalMolecular Therapy
Volume23
Issue number10
DOIs
StatePublished - Oct 1 2015

Fingerprint

Respiratory Syncytial Viruses
Transfer RNA
Antiviral Agents
Virus Replication
MicroRNAs
RNA
Small Untranslated RNA
3' Untranslated Regions
Gene Silencing
Computational Biology
Respiratory Tract Infections
Viruses
Genes
low density lipoprotein receptor-related protein 8
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Genetics
  • Drug Discovery
  • Pharmacology

Cite this

Respiratory Syncytial Virus Utilizes a tRNA Fragment to Suppress Antiviral Responses Through a Novel Targeting Mechanism. / Deng, Junfang; Ptashkin, Ryan N.; Chen, Yu; Cheng, Zhi; Liu, Guangliang; Phan, Thien; Deng, Xiaoling; Zhou, Jiehua; Lee, Inhan; Lee, Yong Sun; Bao, Xiaoyong.

In: Molecular Therapy, Vol. 23, No. 10, 01.10.2015, p. 1622-1629.

Research output: Contribution to journalArticle

Deng, J, Ptashkin, RN, Chen, Y, Cheng, Z, Liu, G, Phan, T, Deng, X, Zhou, J, Lee, I, Lee, YS & Bao, X 2015, 'Respiratory Syncytial Virus Utilizes a tRNA Fragment to Suppress Antiviral Responses Through a Novel Targeting Mechanism', Molecular Therapy, vol. 23, no. 10, pp. 1622-1629. https://doi.org/10.1038/mt.2015.124
Deng, Junfang ; Ptashkin, Ryan N. ; Chen, Yu ; Cheng, Zhi ; Liu, Guangliang ; Phan, Thien ; Deng, Xiaoling ; Zhou, Jiehua ; Lee, Inhan ; Lee, Yong Sun ; Bao, Xiaoyong. / Respiratory Syncytial Virus Utilizes a tRNA Fragment to Suppress Antiviral Responses Through a Novel Targeting Mechanism. In: Molecular Therapy. 2015 ; Vol. 23, No. 10. pp. 1622-1629.
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