S1-Domain RNA Binding Protein (CvfD) Is a New Post-Transcriptional Regulator That Mediates Cold Shock, Phosphate Transport, and Virulence in Streptococcus pneumoniae D39

ABSTRACT: Post-transcriptional gene regulation often involves RNA-binding proteins that modulate mRNA translation and/or stability either directly through protein-RNA interactions or indirectly by facilitating the annealing of small regulatory RNAs (sRNAs). The human pathogen Streptococcus pneumoniae D39 (pneumococcus) does not encode in its genome any homologs to RNA-binding proteins known to be involved in promoting sRNA stability and function, such as Hfq or ProQ, even though it contains genes for at least 112 sRNAs. Instead, the pneumococcal genome contains genes for at least six S1 RNA-binding domain proteins, which includes ribosomal protein S1 (rpsA), polynucleotide phosphorylase (pnpA), RNase R (rnr), and three proteins of unknown function. Here, we characterize the function of one of these conserved, yet uncharacterized S1-domain proteins, SPD_1366, which we have renamed CvfD (Conserved virulence factor D), since loss of this protein results in a attenuation of virulence in a murine pneumonia model. We also report that deletion of cvfD impacts expression of 144 transcripts including the pst1 operon, encoding the phosphate transport system 1 in S. pneumoniae. We further show that CvfD post-transcriptionally regulates the PhoU2 master regulator of the pneumococcal dual phosphate transport system by binding phoU2 mRNA and impacting translation. CvfD not only controls expression of phosphate transporter genes, but also functions as a global regulator impacting cold sensitivity and the expression of sRNAs and genes involved in diverse cellular functions, including manganese uptake and zinc efflux. Together, our data suggest that CvfD exerts a broad impact on pneumococcal physiology and virulence via post-transcriptional gene regulation.

ORGANISM(S): Streptococcus pneumoniae D39

PROVIDER: GSE148867 | GEO | 2020/07/01

REPOSITORIES: GEO