Bacteria employ regulatory RNAs to streamline their gene expression. Global RNA-binding proteins are the hubs in these post-transcriptional gene expression control networks, yet have remained unidentified in one of the dominant phyla of the human gut microbiota, the Bacteroidota. Accumulating evidence now suggests that RRM proteins may be those elusive RBP candidates in these bacteria (PMID: 34379855; 34251866; 39747016). Using RbpB from Bacteroides thetaiotaomicron—currently the best-characterized Bacteroidota RRM protein—as prime model, we will identify the cellular interaction partners of RRM proteins in B. thetaiotaomicron and assess the functional redundancy between individual RRM proteins within and across Bacteroidota. In parallel, reverse genetics will help uncover the physiological processes dependent on RRM proteins in B. thetaiotaomicron and mutational analysis will pinpoint functionally critical moieties of RRM proteins. We will further investigate the mode-of-action of a selected Bacteroidota RRM protein and elucidate its role during colonization of the mammalian gut. The derived insights may help to fill some of the current major gaps in our understanding of post-transcriptional gene expression control in predominant gut microbiota members and could boost ongoing endeavors to harness gut Bacteroides as tools and targets for microbiota-centric intervention therapies.