An mRNA-mRNA Interaction Couples Expression of a Virulence Factor and Its Chaperone in Listeria monocytogenes

Abstract

Summary: Bacterial pathogens often employ RNA regulatory elements located in the 5′ untranslated regions (UTRs) to control gene expression. Using a comparative structural analysis, we examine the structure of 5′ UTRs at a global scale in the pathogenic bacterium Listeria monocytogenes under different conditions. In addition to discovering an RNA thermoswitch and detecting simultaneous interaction of ribosomes and small RNAs with mRNA, we identify structural changes in the 5′ UTR of an mRNA encoding the post-translocation chaperone PrsA2 during infection conditions. We demonstrate that the 5′ UTR of the prsA2 mRNA base pairs with the 3′ UTR of the full-length hly mRNA encoding listeriolysin O, thus preventing RNase J1-mediated degradation of the prsA2 transcript. Mutants lacking the hly-prsA2 interaction exhibit reduced virulence properties. This work highlights an additional level of RNA regulation, where the mRNA encoding a chaperone is stabilized by the mRNA encoding its substrate. : By using a comparative structural analysis method targeting 5′ untranslated regions, Ignatov et al. identify different RNA-based regulatory mechanisms such as an RNA thermoswitch, a small RNA (sRNA)-mRNA interaction, and strikingly, an mRNA-mRNA interaction. Keywords: RNA structure, 5′ untranslated regions, RNA thermosensor, small RNA, mRNA-mRNA interaction, listeriolysin O, PrsA2 chaperone, PrfA