Secretable Small RNAs via Outer Membrane Vesicles in Periodontal Pathogens

Secretable Small RNAs via Outer Membrane Vesicles in Periodontal Pathogens
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DOI:
10.1177/0022034516685071
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发表时间:
2017-04-01
影响因子:
7.6
通讯作者:
Lee, H. -J.
Lee, H. -J.
中科院分区:
医学1区
文献类型:
--
作者:
Choi, J. -W.;Kim, S. -C.;Lee, H. -J.

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microRNA(miRNAs)是真核生物基因表达的主要调控因子。然而,与真核miRNA(18-22个核苷酸)大小相当的细菌RNA很少受到关注。最近,在几种细菌中也发现了一类大小与miRNA相似的新型小RNA(miRNA大小,小RNA或msRNA)。与miRNAs一样,msRNAs的长度约为15至25个核苷酸,并且预测它们的前体形成发夹环二级结构。在这里,我们确定了牙周病原体伴放线菌聚集杆菌,牙龈卟啉单胞菌和齿垢密螺旋体中的msRNAs。我们使用深度测序方法检查了这些msRNAs,并通过生物信息学分析表征了数十种msRNAs。选择高表达的msRNA用于进一步验证。研究结果表明,这类小RNA在生命的各个领域都很保守。实际上,检测到经由细菌外膜囊泡(OMV)分泌的msRNA。还观察到细菌OMV将RNA递送到真核细胞中的能力。OMV中的这些msRNA使我们能够识别它们潜在的人类免疫相关靶基因。此外,我们发现外源性msRNAs可以抑制Jurkat T细胞中某些细胞因子的表达。我们认为msRNA可能作为新型细菌信号分子发挥作用,介导细菌与人类的相互作用。此外,本研究可能为牙周病的细菌致病机制提供新的见解。
MicroRNAs (miRNAs) have been shown to be major regulators of eukaryotic gene expression. However, bacterial RNAs comparable in size to eukaryotic miRNAs (18-22 nucleotides) have received little attention. Recently, a novel class of small RNAs similar in size to miRNAs (miRNA-size, small RNAs or msRNAs) have also been found in several bacteria. Like miRNAs, msRNAs are approximately 15 to 25 nucleotides in length, and their precursors are predicted to form a hairpin loop secondary structure. Here, we identified msRNAs in the periodontal pathogens Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Treponema denticola. We examined these msRNAs using a deep sequencing method and characterized dozens of msRNAs through bioinformatic analysis. Highly expressed msRNAs were selected for further validation. The findings suggest that this class of small RNAs is well conserved across the domains of life. Indeed, msRNAs secreted via bacterial outer membrane vesicles (OMVs) were detected. The ability of bacterial OMVs to deliver RNAs into eukaryotic cells was also observed. These msRNAs in OMVs allowed us to identify their potential human immune-related target genes. Furthermore, we found that exogenous msRNAs could suppress expression of certain cytokines in Jurkat T cells. We propose msRNAs may function as novel bacterial signaling molecules that mediate bacteria-to-human interactions. Furthermore, this study may provide fresh insight into bacterial pathogenic mechanisms of periodontal diseases.