3' UTR-mediated regulation of a protein chaperone by the pspA mRNA in Streptococcus pneumoniae.

RNA-mediated control of virulence gene expression plays a crucial role in many pathogenic bacteria. However, our understanding of these processes in Streptococcus pneumoniae, a major human pathogen, remains limited. Here we discover a novel regulatory element located in the 3'-untranslated region (3' UTR) of the mRNA encoding a major pneumococcal virulence factor, pneumococcal surface protein A (PspA). Quantitative proteomics and western blot analysis reveal that this 3' UTR acts as a trans-acting riboregulatory element, modulating the expression of the protein chaperone, Caseinolytic protease L (ClpL), in a temperature-dependent manner. We show that it is the full-length pspA mRNA, and not the pspA-3'-located processed F5 RNA, which is involved in the regulation of ClpL expression, with the sRNA-interacting exoribonuclease Cbf1 playing an important role. Furthermore, complement deposition assays show that the regulatory pspA-3' UTR contributes to inhibition of complement C3 deposition in a PspA-independent and temperature-dependent manner. This discovery adds a new dimension to our understanding of PspA's role in bacterial virulence, highlighting an intricate layer of RNA-mediated regulation that contributes to the pathogenicity of S. pneumoniae.