A variable homopolymeric G-repeat defines small RNA-mediated posttranscriptional regulation of a chemotaxis receptor in Helicobacter pylori.
Phase variation of hypermutable simple sequence repeats (SSRs) is a widespread and stochastic mechanism to generate phenotypic variation within a population and thereby contributes to host adaptation of bacterial pathogens. Although several examples of SSRs that affect transcription or coding potential have been reported, we now show that a SSR also impacts small RNA-mediated posttranscriptional regulation. Based on in vitro and in vivo analyses, we demonstrate that a variable homopolymeric G-repeat in the leader of the TlpB chemotaxis receptor mRNA of the human pathogen Helicobacter pylori is directly targeted by a small RNA (sRNA), RepG (Regulator of polymeric G-repeats). Whereas RepG sRNA is highly conserved, the tlpB G-repeat length varies among diverse H. pylori strains, resulting in strain-specific RepG-mediated tlpB regulation. Based on modification of the G-repeat length within one strain, we demonstrate that the G-repeat length determines posttranscriptional regulation and can mediate both repression and activation of tlpB through RepG. In vitro translation assays show that this regulation occurs at the translational level and that RepG influences tlpB translation dependent on the G-repeat length. In contrast to the digital ON-OFF switches through frame-shift mutations within coding sequences, such modulation of posttranscriptional regulation allows for a gradual control of gene expression. This connection to sRNA-mediated posttranscriptional regulation might also apply to other genes with SSRs, which could be targeting sites of cis- or trans-encoded sRNAs, and thereby could facilitate host adaptation through sRNA-mediated fine-tuning of virulence gene expression.
Research Center for Infectious Diseases (ZINF), University of Würzburg, 97080 Würzburg, Germany.
Sandy R
SR
Pernitzsch
Stephan M
SM
Tirier
Dagmar
D
Beier
Cynthia M
CM
Sharma
D001483:Base Sequence; D002633:Chemotaxis / Q000235:genetics*; D004269:DNA, Bacterial; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D016480:Helicobacter pylori / Q000235:genetics*; D008969:Molecular Sequence Data; D012323:RNA Processing, Post-Transcriptional; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid
D004269:DNA, Bacterial
homopolymeric repeat; noncoding RNA