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. Small non-coding RNAs (
sncRNAs) are known to play important roles in almost all biological processes. In the context of
viral infections,
sncRNAs have been shown to regulate 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 recently found that nasopharyngeal swabs (NPS) samples from SARS-CoV-2 positive and negative subjects show a significant difference in
sncRNA profiles. There are about 166 SARS-CoV-2-impacted
sncRNAs. Among them, tRFs are the most significantly affected and almost all impacted tRFs are derived from the 5'-end of tRNAs (tRF5). Using a modified qRT-PCR, which was recently developed to specifically quantify tRF5s by isolating the tRF signals from its corresponding parent
tRNA signals, we validated that tRF5s derived from
tRNA GluCTC (tRF5-GluCTC), LysCTT (tRF5-LysCTT), ValCAC (tRF5-ValCAC), CysGCA (tRF5-CysGCA) and GlnCTG (tRF5-GlnCTG) are enhanced in NPS samples of SARS-CoV2 patients and SARS-CoV2-infected airway epithelial cells. In addition to host-derived ncRNAs, we also identified several
sncRNAs derived from the virus (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.