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

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

He X1, Li F2,3, Bor B1, Koyano K4,5, Cen L1, Xiao X4,5, Shi W1, Wong DTW2,4,5.

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1 The Forsyth Institute, Cambridge, MA, USA.
2 School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
3 Institute of Diagnostic in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China.
4 Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
5 Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA.


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.


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

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