Unique tRNA Fragment Upregulation with SARS-CoV-2 but Not with SARS-CoV Infection

Isabella Imirowicz, Azeem Saifee, Leanne Henry, Leo Tunkle, Alexander Popescu, Philip Huang, Jibiana Jakpor, Ava Barbano, Rohit Goru, Audrey Gunawan, Maria Sicilia, Mori Ono, Xiaoyong Bao, Inhan Lee

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Unlike other coronaviruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly infected the global population, with some suffering long-term effects. Thanks to extensive data on SARS-CoV-2 made available through global, multi-level collaborative research, investigators are getting closer to understanding the mechanisms of SARS-CoV-2 infection. Here, using publicly available total and small RNAseq data of Calu3 cell lines, we conducted a comparative analysis of the changes in tRNA fragments (tRFs; regulatory small noncoding RNAs) in the context of severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 infections. We found extensive upregulation of multiple tRFs in SARS-CoV-2 infection that was not present in SARS-CoV or other virus infections our group has studied. By comparing the total RNA changes in matching samples, we identified significant downregulation of TRDMT1 (tRNA methyltransferase), only in SARS-CoV-2 infection, a potential upstream event. We further found enriched neural functions among downregulated genes with SARS-CoV-2 infection. Interestingly, theoretically predicted targets of the upregulated tRFs without considering mRNA expression data are also enriched in neural functions such as axon guidance. Based on a combination of expression data and theoretical calculations, we propose potential targets for tRFs. For example, among the mRNAs downregulated with SARS-CoV-2 infection (but not with SARS-CoV infection), SEMA3C is a theoretically calculated target of multiple upregulated tRFs and a ligand of NRP1, a SARS-CoV-2 receptor. Our analysis suggests that tRFs contribute to distinct neurological features seen in SARS-CoV-2.

Original languageEnglish (US)
Article number399
JournalInternational journal of molecular sciences
Issue number1
StatePublished - Jan 2024


  • COVID-19
  • long COVID
  • neural function
  • NRP1
  • SARS
  • SARS-CoV
  • SARS-CoV-2
  • SEMA3C
  • small ncRNA
  • tRF5

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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