title: Synergies between RNA degradation and trans-translation in Streptococcus pneumoniae: cross regulation and co-transcription of RNase R and SmpB.
abstract: BACKGROUND
  Ribonuclease R (RNase R) is an exoribonuclease that recognizes and degrades a wide range of RNA molecules. It is a stress-induced protein shown to be important for the establishment of virulence in several pathogenic bacteria. RNase R has also been implicated in the trans-translation process. Transfer-messenger RNA (tmRNA/SsrA RNA) and SmpB are the main effectors of trans-translation, an RNA and protein quality control system that resolves challenges associated with stalled ribosomes on non-stop mRNAs. Trans-translation has also been associated with deficiencies in stress-response mechanisms and pathogenicity.
  
  
  RESULTS
  In this work we study the expression of RNase R in the human pathogen Streptococcus pneumoniae and analyse the interplay of this enzyme with the main components of the trans-translation machinery (SmpB and tmRNA/SsrA). We show that RNase R is induced after a 37°C to 15°C temperature downshift and that its levels are dependent on SmpB. On the other hand, our results revealed a strong accumulation of the smpB transcript in the absence of RNase R at 15°C. Transcriptional analysis of the S. pneumoniae rnr gene demonstrated that it is co-transcribed with the flanking genes, secG and smpB. Transcription of these genes is driven from a promoter upstream of secG and the transcript is processed to yield mature independent mRNAs. This genetic organization seems to be a common feature of Gram positive bacteria, and the biological significance of this gene cluster is further discussed.
  
  
  CONCLUSIONS
  This study unravels an additional contribution of RNase R to the trans-translation system by demonstrating that smpB is regulated by this exoribonuclease. RNase R in turn, is shown to be under the control of SmpB. These proteins are therefore mutually dependent and cross-regulated. The data presented here shed light on the interactions between RNase R, trans-translation and cold-shock response in an important human pathogen.
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da República, Oeiras 2780-157, Portugal.
authors.forename: Ricardo N
authors.initials: RN
authors.lastname: Moreira
authors.forename: Susana
authors.initials: S
authors.lastname: Domingues
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Viegas
authors.forename: Mónica
authors.initials: M
authors.lastname: Amblar
authors.forename: Cecília M
authors.initials: CM
authors.lastname: Arraiano
mesh_terms: D005095:Exoribonucleases / Q000096:biosynthesis*; D015964:Gene Expression Regulation, Bacterial; D014176:Protein Biosynthesis; D020871:RNA Stability; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D013296:Streptococcus pneumoniae / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D013696:Temperature; D014158:Transcription, Genetic
chemical_list: D016601:RNA-Binding Proteins; C430328:small protein B; D005095:Exoribonucleases; C080868:ribonuclease R