Small proteins and dual RNA regulators regulating collective behaviors and carbon metabolism in Vibrio cholerae

• Applicant: Professor Dr. Kai Papenfort
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 379644638

The annotation of microbial genomes typically relies on the prediction of open reading frames (ORFs) with a minimal length requirement. While setting a lower limit for ORF length has led to a strong decrease in false positive gene annotations, it also resulted in an underrepresentation of small protein genes that we now know play important roles in microbial physiology. This strategy also failed to identify the so-called nested ORFs produced from within larger ORFs, as well as dual RNA regulators, which contain a base-pairing function and a small protein. In the previous funding period of this program, we have used ribosome profiling to identify small proteins in the major human pathogen, Vibrio cholerae. These studies resulted in the discovery of dozens of small proteins, including several examples of nested ORFs, and dual RNA regulators. Detailed analyses of one dual RNA, named VcdR (Vibrio cholerae dual RNA regulator), revealed a central role of this regulator in carbon metabolism control of V. cholerae. We next aim to understand the molecular underpinnings of VcdR-mediated gene regulation, as well as the roles of other small proteins in important collective behaviors such as quorum sensing, biofilm formation and virulence. Together, the work outlined in this proposal will further expand our view on the functions of small proteins in V. cholerae with a focus on yet only poorly studied examples contained in dual RNAs and nested ORFs.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2002: Small Proteins in Prokaryotes, an Unexplored World