Riboregulation in Neisseria meningitidis

Neisseria meningitidis (the meningococcus) is primarily a commensal of the human oropharynx that sporadically causes septicemia and meningitis. Meningococci adapt to diverse local host conditions that differ in nutrient supply such as the nasopharynx, blood and cerebrospinal fluid by changing metabolism and protein repertoire. Post-transcriptional riboregulation by small non-coding RNAs (sRNAs) are increasingly recognized to play a vital role in these metabolic adaptations.
In this thesis, we first investigated the regulon of the alternative sigma factor E by employing next-generation sequencing of both the genome and the transcriptome of N. meningitidis wildtype and an overexpression mutant. Its small regulatory repertoire compared to E. coli and its lack of regulating proteins involved in the outer membrane stress response is a prime example of divergent evolution of superficially similar regulatory systems in these two gram-negative bacteria. Second, the chaperon protein Hfq and its role in riboregulation by facilitating RNA-RNA interactions between a sRNA and its mRNA target(s) was investigated by studying its regulatory proteome in depth. Finally, the regulatory roles of two sRNAs, NmsRs and NrrF are described; showing their extensive involvement in the related cell biological processes of carbohydrate metabolism and oxidative phosphorylation by simultaneously downregulating multiple enzymes involved in these pathways.
In conclusion, small RNAs like the NmsRs and NrrF can be transcribed quickly, have a relatively low biological cost and can act immediately on an already existing cellular pool of mRNA targets. These factors make them ideally suited to enable the meningococcus to respond to changes in the environment.