1 The Forsyth Institute, Cambridge, MA, USA.
2 School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
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.
人类宿主与其相关微生物群落的共同进化导致了复杂的相互作用，以维持微妙的动态平衡。新出现的证据表明，除了小分子、肽和蛋白质外，小调控非编码 RNA（sRNA）可能在跨域相互作用中发挥重要作用。在这项研究中，我们在人类唾液 sRNA 中发现了多种宿主转移 RNA 衍生的小 RNA（tsRNA）。我们选择了 2 种 tsRNA（tsRNA-000794 和 tsRNA-020498）进行进一步研究，因为它们与一组革兰氏阴性口腔细菌（包括核梭杆菌）的特定 tRNA 具有很高的序列相似性，核梭杆菌是口腔共生菌和机会性病原体。我们表明，核梭杆菌的存在会触发人正常口腔角质形成细胞通过外体释放 tsRNA-000794 和 tsRNA-020498。此外，这两种 tsRNA 候选物都对核梭杆菌表现出生长抑制作用，可能是通过干扰细菌蛋白质生物合成，但不影响与核梭杆菌基因组不携带与任何一种 tsRNA 高度相似序列的健康相关口腔革兰氏阳性菌——草绿色链球菌的生长。我们的数据为宿主衍生的 tsRNA 在微生物-宿主相互作用中的调节作用提供了第一个证据。
