Project description
Insight into bacterial RNA-binding proteins
Ribonucleic acid (RNA)-binding proteins (RBPs) are emerging as key regulators of post-transcriptional processes impacting important biological functions. RBPs contain RNA-binding domains or highly disordered regions responsible for interacting with RNA molecules such as transcripts. The EU-funded bacRBP project focuses on unexplored unconventional RBPs in bacteria, that lack RNA-binding domains. Researchers will employ a recently developed innovative method for capturing and studying such RBPs. The scope is to identify the RBPs implicated in stress responses and in infection. Project results will provide fundamental knowledge on cellular control and pave the way for the design of novel antimicrobial treatments.
Objective
All organisms use diverse modes of cellular control as they cope with changing environments. Central to these processes are RNA-binding proteins (RBPs) that impact the stability, translation, or localization of bound RNAs. While RBPs typically have distinct RNA-binding domains, a growing number of proteins that lack these domains are found to interact with RNA as well. In prokaryotes, such unconventional RBPs remain largely unexplored, in part because methods for global RNA interactome capture (RIC) in bacteria are missing. My group recently made a breakthrough in developing a novel RIC approach for bacteria that relies on primary transcript capture (CoCAP). Our pilot study successfully captured known RBPs but also uncovered numerous new RBP candidates, including metabolic or cell division proteins. We also identified a pair of widespread KH-domain proteins (KhpA/B) with links to the RNA degradosome and cell division. This points towards a wealth of unexplored RBPs involved in cellular control in bacteria.
My ERC CoG proposal aims to explore the identity and functional diversity of novel RBPs in bacteria. My overarching hypothesis is that a vast, unexplored universe of unconventional RBPs exists in bacteria that play crucial roles in cellular physiology. I will tackle this through three objectives leveraging two model bacteria (Salmonella and Campylobacter) with different sets of canonical RBPs. I propose to:
1) Elucidate bacterial primary RBPomes during stress- and infection-relevant conditions.
2) Identify mechanisms and cellular functions of two widely conserved KH-domain RBPs.
3) Determine how cell division RBPs influence and are influenced by bound RNAs.
Our proposed work will provide a broadly applicable method for primary RBPome capture and vastly expand the set of bacterial RBPs. Their characterization in turn will reveal new layers of cellular control and establish new targets for industrial strain engineering and antimicrobial treatments.
Fields of science
Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
97070 Wuerzburg
Germany