Human tRNA-Derived Small RNAs Modulate Host-Oral Microbial Interactions

J Dent Res. 2018 Oct;97(11):1236-1243. doi: 10.1177/0022034518770605. Epub 2018 Apr 27.


Coevolution of the human host and its associated microbiota has led to sophisticated interactions to maintain a delicate homeostasis. Emerging evidence suggests that in addition to small molecules, peptides, and proteins, small regulatory noncoding RNAs (sRNAs) might play an important role in cross-domain interactions. In this study, we revealed the presence of diverse host transfer RNA-derived small RNAs (tsRNAs) among human salivary sRNAs. We selected 2 tsRNAs (tsRNA-000794 and tsRNA-020498) for further study based on their high sequence similarity to specific tRNAs from a group of Gram-negative oral bacteria, including Fusobacterium nucleatum, a key oral commensal and opportunistic pathogen. We showed that the presence of F. nucleatum triggers exosome-mediated release of tsRNA-000794 and tsRNA-020498 by human normal oral keratinocyte cells. Furthermore, both tsRNA candidates exerted a growth inhibition effect on F. nucleatum, likely through interference with bacterial protein biosynthesis, but did not affect the growth of Streptococcus mitis, a health-associated oral Gram-positive bacterium whose genome does not carry sequences bearing high similarity to either tsRNA. Our data provide the first line of evidence for the modulatory role of host-derived tsRNAs in the microbial-host interaction.

Keywords: antimicrobials; cross-domain interactions; microbial-host interaction; oral microbiome; sRNAs; tsRNAs.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Fusobacterium nucleatum / growth & development
  • Fusobacterium nucleatum / metabolism
  • Host Microbial Interactions* / physiology
  • Humans
  • Keratinocytes / metabolism
  • Mouth / microbiology*
  • RNA, Small Untranslated / physiology*
  • RNA, Transfer / physiology*
  • Saliva / metabolism


  • RNA, Small Untranslated
  • RNA, Transfer