Department of Medicine, NYU Grossman School of Medicine, 450 East 29th St., Room 341, New York, New York 10016, United States.
Department of Chemistry, New York University, 100 Washington Square East, Silver Building, New York, New York 10003, United States.
J Phys Chem B. 2024 May 9;128(18):4336-4343. doi: 10.1021/acs.jpcb.4c00267. Epub 2024 Apr 24.
Riboswitches are widely distributed, conserved RNAs which regulate metabolite levels in bacterial cells through direct, noncovalent binding of their cognate metabolite. Various riboswitch families are highly enriched in gut bacteria, suggestive of a symbiotic relationship between the host and bacteria. Previous studies of the distribution of riboswitches have examined bacterial taxa broadly. Thus, the distribution of riboswitches associated with bacteria inhabiting the intestines of healthy individuals is not well understood. To address these questions, we survey the gut microbiome for riboswitches by including an international database of prokaryotic genomes from the gut samples. Using Infernal, a program that uses RNA-specific sequence and structural features, we survey this data set using existing riboswitch models. We identify 22 classes of riboswitches with vitamin cofactors making up the majority of riboswitch-associated pathways. Our finding is reproducible in other representative databases from the oral as well as the marine microbiomes, underscoring the importance of thiamine pyrophosphate, cobalamin, and flavin mononucleotide in gene regulation. Interestingly, riboswitches do not vary significantly across microbiome representatives from around the world despite major taxonomic differences; this suggests an underlying conservation. Further studies elucidating the role of bacterial riboswitches in the host metabolome are needed to illuminate the consequences of our finding.
Riboswitches 是广泛分布且保守的 RNA 分子,通过与其同源代谢物的直接非共价结合来调节细菌细胞中的代谢物水平。各种 Riboswitch 家族在肠道细菌中高度富集,提示宿主和细菌之间存在共生关系。以前对 Riboswitch 分布的研究广泛地检查了细菌分类群。因此,与居住在健康个体肠道中的细菌相关的 Riboswitch 的分布尚不清楚。为了解决这些问题,我们通过包括来自肠道样本的国际原核基因组数据库,调查了肠道微生物组中的 Riboswitch。我们使用 Infernal,这是一个使用 RNA 特定序列和结构特征的程序,使用现有的 Riboswitch 模型对该数据集进行了调查。我们确定了 22 类与维生素辅因子相关的 Riboswitch,这些辅因子构成了 Riboswitch 相关途径的大部分。我们的发现可以在口腔和海洋微生物组的其他代表性数据库中重现,这强调了硫胺素焦磷酸、钴胺素和黄素单核苷酸在基因调控中的重要性。有趣的是,尽管存在主要的分类群差异,但 Riboswitch 在来自世界各地的微生物组代表中并没有显著变化;这表明存在潜在的保守性。进一步阐明细菌 Riboswitch 在宿主代谢组中的作用的研究需要阐明我们发现的后果。