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Parent tRNA Modification Status Determines the Induction of Functional tRNA-Derived RNA by Respiratory Syncytial Virus Infection.
Choi, Eun-Jin; Wu, Wenzhe; Zhang, Ke; Yuan, Xiaohong; Deng, Junfang; Ismail, Deena; Buck, Darby L; Thomason, Kerrie S; Garofalo, Roberto P; Zhang, Shenglong; Bao, Xiaoyong.
  • Choi EJ; Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Wu W; Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Zhang K; Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Yuan X; Department of Biological and Chemical Science, New York Institute of Technology, New York, NY 10023, USA.
  • Deng J; Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Ismail D; Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Buck DL; Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Thomason KS; Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Garofalo RP; Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Zhang S; Institute of Translational Science, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Bao X; Institute for Human Infections Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA.
Viruses ; 15(1)2022 Dec 24.
Article in English | MEDLINE | ID: covidwho-2216911
ABSTRACT
tRNA-derived RNA fragments (tRFs) are a recently discovered family of small noncoding RNAs (sncRNAs). We previously reported that respiratory syncytial virus (RSV) infection induces functional tRFs, which are derived from a limited subset of parent tRNAs, in airway epithelial cells. Such induction is also observed in nasopharyngeal wash samples from RSV patients and correlates to RSV genome copies, suggesting a clinical significance of tRFs in RSV infection. This work also investigates whether the modification of parent tRNAs is changed by RSV to induce tRFs, using one of the most inducible tRFs as a model. We discovered that RSV infection changed the methylation modification of adenine at position 57 in tRNA glutamic acid, with a codon of CTC (tRNA-GluCTC), and the change is essential for its cleavage. AlkB homolog 1, a previously reported tRNA demethylase, appears to remove methyladenine from tRNA-GluCTC, prompting the subsequent production of tRFs from the 5'-end of tRNA-GluCTC, a regulator of RSV replication. This study demonstrates for the first time the importance of post-transcriptional modification of tRNAs in tRF biogenesis following RSV infection, providing critical insights for antiviral strategy development.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Syncytial Virus Infections / RNA, Small Untranslated Type of study: Prognostic study Limits: Humans Language: English Year: 2022 Document Type: Article Affiliation country: V15010057

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Syncytial Virus Infections / RNA, Small Untranslated Type of study: Prognostic study Limits: Humans Language: English Year: 2022 Document Type: Article Affiliation country: V15010057