Parent tRNA Modification Status Determines the Induction of Functional tRNA-Derived RNA by Respiratory Syncytial Virus Infection

Eun Jin Choi, Wenzhe Wu, Ke Zhang, Xiaohong Yuan, Junfang Deng, Deena Ismail, Darby L. Buck, Kerrie S. Thomason, Roberto P. Garofalo, Shenglong Zhang, Xiaoyong Bao

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article number57
JournalViruses
Volume15
Issue number1
DOIs
StatePublished - Jan 2023

Keywords

  • RSV replication
  • tRF
  • tRNA modification

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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