Changes of Small Non-coding RNAs by Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Wenzhe Wu, Eun Jin Choi, Binbin Wang, Ke Zhang, Awadalkareem Adam, Gengming Huang, Leo Tunkle, Philip Huang, Rohit Goru, Isabella Imirowicz, Leanne Henry, Inhan Lee, Jianli Dong, Tian Wang, Xiaoyong Bao

Research output: Contribution to journalArticlepeer-review


The ongoing pandemic of coronavirus disease 2019 (COVID-19), which results from the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a significant global public health threat, with molecular mechanisms underlying its pathogenesis largely unknown. In the context of viral infections, small non-coding RNAs (sncRNAs) are known to play important roles in regulating the host responses, viral replication, and host-virus interaction. Compared with other subfamilies of sncRNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), tRNA-derived RNA fragments (tRFs) are relatively new and emerge as a significant regulator of host-virus interactions. Using T4 PNK‐RNA‐seq, a modified next-generation sequencing (NGS), we found that sncRNA profiles in human nasopharyngeal swabs (NPS) samples are significantly impacted by SARS-CoV-2. Among impacted sncRNAs, tRFs are the most significantly affected and most of them are derived from the 5′-end of tRNAs (tRF5). Such a change was also observed in SARS-CoV-2-infected airway epithelial cells. In addition to host-derived ncRNAs, we also identified several small virus-derived ncRNAs (svRNAs), among which a svRNA derived from CoV2 genomic site 346 to 382 (sv-CoV2-346) has the highest expression. The induction of both tRFs and sv-CoV2-346 has not been reported previously, as the lack of the 3′-OH ends of these sncRNAs prevents them to be detected by routine NGS. In summary, our studies demonstrated the involvement of tRFs in COVID-19 and revealed new CoV2 svRNAs.

Original languageEnglish (US)
Article number821137
JournalFrontiers in Molecular Biosciences
StatePublished - Feb 23 2022


  • SARS-CoV-2
  • SARS-CoV-2-derived sncRNAs
  • TRF
  • tRF5DC
  • viral replication and SARS-CoV-2-derived sncRNAs

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)


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