title: Respiratory Syncytial Virus Utilizes a tRNA Fragment to Suppress Antiviral Responses Through a Novel Targeting Mechanism.
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.
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA.|Department of Hepatobiliary Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, China.
authors.forename: Junfang
authors.initials: J
authors.lastname: Deng
authors.affiliation: miRcore, Ann Arbor, Michigan, USA.|Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Ryan N
authors.initials: RN
authors.lastname: Ptashkin
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA.|Department of Otorhinolaryngology, Sixth Affiliated Hospital, Sun Yat-Sen University, Guangdong, China.
authors.forename: Guangliang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Thien
authors.initials: T
authors.lastname: Phan
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Jiehua
authors.initials: J
authors.lastname: Zhou
authors.affiliation: miRcore, Ann Arbor, Michigan, USA.
authors.forename: Inhan
authors.initials: I
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Yong Sun
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA.|Institute for Translational Science, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Bao
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D058727:RNA, Small Untranslated / Q000737:chemistry / Q000235:genetics; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics; D018113:Respiratory Syncytial Virus, Human / Q000502:physiology; D014162:Transfection; D015678:Viral Structural Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics
chemical_list: D026502:LDL-Receptor Related Proteins; C529603:P protein, human respiratory syncytial virus; D058727:RNA, Small Untranslated; D015678:Viral Structural Proteins; C098773:low density lipoprotein receptor-related protein 8; D012343:RNA, Transfer