Project Details
Projekt
Functional characterization of Bacteroidota RRM proteins: a prevalent family of RNA-binding proteins in the human gut microbiota
Applicant
Professor Alexander Westermann, Ph.D.
Subject Area
Metabolism, Biochemistry and Genetics of Microorganisms
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 564322798
The Bacteroidota represent a dominant phylum of the human gut microbiota and benefit their mammalian host in various ways. Generally, the evolutionary success of bacteria depends on their ability to rapidly adapt to changing environmental conditions. The changes in gene expression are oftentimes brought about at the post-transcriptional level, by so-called small regulatory RNAs (sRNAs) in conjunction with global RNA-binding proteins (RBPs). While key commensals of the intestinal ecosystem such as Bacteroidota have long been neglected in the sRNA field, recent studies began to dissect the RNA biology of gut Bacteroidota and already provided novel insights into bacterial sRNA-mediated regulations. However, the identity and role of global RBPs in gut Bacteroidota has remained elusive. Only very recently, my lab identified the first known global RBP in this bacterial phylum, termed RbpB. RbpB belongs to the family of RNA recognition motif (RRM)-containing proteins, which is prevalent in nearly all Bacteroidota species. We have functionally characterized RbpB in Bacteroides thetaiotaomicron and demonstrated that this RRM protein binds hundreds of mRNAs and dozens of sRNAs in vivo. A B. thetaiotaomicron mutant devoid of RbpB was ineffective in colonizing the mammalian gastrointestinal tract in a host diet-dependent manner. However, it remains unclear to what extent these findings may be generalizable to other RRM proteins in B. thetaiotaomicron and other Bacteroidota members. The present project investigates the cellular functions of RRM proteins in different Bacteroidota species. 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 Bacteroidota as tools and targets for microbiota-centric intervention therapies.
DFG Programme
Priority Programmes
Co-Investigators
Professor Dr. Thomas Clavel; Dr. Mikhail Savitski, Ph.D.
