Comparative genomics provides structural and functional insights into Bacteroides RNA biology. Issue 1 (28th August 2021) - Prezza, Gianluca
Abstract: Bacteria employ noncoding RNA molecules for a wide range of biological processes, including scaffolding large molecular complexes, catalyzing chemical reactions, defending against phages, and controlling gene expression. Secondary structures, binding partners, and molecular mechanisms have been determined for numerous small noncoding RNAs (sRNAs) in model aerobic bacteria. However, technical hurdles have largely prevented analogous analyses in the anaerobic gut microbiota. While experimental techniques are being developed to investigate the sRNAs of gut commensals, computational tools and comparative genomics can provide immediate functional insight. Here, using Bacteroides thetaiotaomicron as a representative microbiota member, we illustrate how comparative genomics improves our understanding of RNA biology in an understudied gut bacterium. We investigate putative RNA‐binding proteins and predict a Bacteroides cold‐shock protein homolog to have an RNA‐related function. We apply an in silico protocol incorporating both sequence and structural analysis to determine the consensus structures and conservation of nine Bacteroides noncoding RNA families. Using structure probing, we validate and refine these predictions and deposit them in the Rfam database. Through synteny analyses, we illustrate how genomic coconservation can serve as a predictor of sRNA function. Altogether, this work showcases the power of RNA informatics for investigating the RNA biology of anaerobic microbiota members. Abstract : Most of our knowledge of bacterial regulatory RNAs and their associated proteins stems from model organisms such as Escherichia coli and Salmonella enterica . In contrast, the RNA biology of Bacteroides spp.—an important component of the human gut microbiota—is significantly understudied. In this foundational study, we leverage comparative genomics combined with experimental characterization to predict RNA‐binding proteins and determine the structure and conservation of noncoding RNA families in these medically important anaerobic bacteria.