RNase Y-mediated regulation of the streptococcal pyrogenic exotoxin B

RNA Biol. 2018;15(10):1336-1347. doi: 10.1080/15476286.2018.1532253. Epub 2018 Oct 18.

Abstract

Endoribonuclease Y (RNase Y) is a crucial regulator of virulence in Gram-positive bacteria. In the human pathogen Streptococcus pyogenes, RNase Y is required for the expression of the major secreted virulence factor streptococcal pyrogenic exotoxin B (SpeB), but the mechanism involved in this regulation remains elusive. Here, we demonstrate that the 5' untranslated region of speB mRNA is processed by several RNases including RNase Y. In particular, we identify two RNase Y cleavage sites located downstream of a guanosine (G) residue. To assess whether this nucleotide is required for RNase Y activity in vivo, we mutated it and demonstrate that the presence of this G residue is essential for the processing of the speB mRNA 5' UTR by RNase Y. Although RNase Y directly targets and processes speB, we show that RNase Y-mediated regulation of speB expression occurs primarily at the transcriptional level and independently of the processing in the speB mRNA 5' UTR. To conclude, we demonstrate for the first time that RNase Y processing of an mRNA target requires the presence of a G. We also provide new insights on the speB 5' UTR and on the role of RNase Y in speB regulation.

Keywords: 5′ untranslated region; RNase Y; Streptococcus pyogenes; speB; transcriptional regulation; virulence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics
  • Amino Acid Sequence / genetics
  • Bacterial Proteins / genetics*
  • Exotoxins / genetics*
  • Gene Expression Regulation, Bacterial / genetics
  • Guanosine / metabolism
  • Humans
  • Ribonucleases / genetics*
  • Streptococcal Infections / genetics*
  • Streptococcal Infections / metabolism
  • Streptococcal Infections / microbiology
  • Streptococcus pyogenes / genetics*
  • Streptococcus pyogenes / pathogenicity
  • Virulence Factors / genetics

Substances

  • 5' Untranslated Regions
  • Bacterial Proteins
  • Exotoxins
  • Virulence Factors
  • erythrogenic toxin
  • Guanosine
  • Ribonucleases

Grant support

We thank the Alexander von Humboldt Foundation [AvH Professorship to E.C.], the Helmholtz Association, the Max Planck Society, the Max Planck Foundation, the Göran Gustafsson Foundation [Göran Gustafsson Prize to E.C.], the Kempe Foundation, Umeå University [Dnr: 223-2836-10] and the Swedish Research Council [K2013-57X-21436-04-3] for funding this study.