RT Journal Article
SR Electronic
T1 A genetic selection reveals functional metastable structures embedded in a toxin-encoding mRNA
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 615682
DO 10.1101/615682
A1 Sara Masachis
A1 Nicolas J. Tourasse
A1 Claire Lays
A1 Marion Faucher
A1 Sandrine Chabas
A1 Isabelle Iost
A1 Fabien Darfeuille
YR 2019
UL http://biorxiv.org/content/early/2019/04/22/615682.abstract
AB Post-transcriptional regulation plays important roles to finely tune gene expression in bacteria. In particular, regulation of type I toxin-antitoxin (TA) systems is achieved through sophisticated mechanisms involving toxin mRNA folding. Here, we set up a genetic approach to decipher the molecular underpinnings behind the regulation of a type I TA in Helicobacter pylori. We used the lethality induced by chromosomal inactivation of the antitoxin to select mutations that suppress toxicity. We found that single point mutations are sufficient to allow cell survival. Mutations located either in the 5’ untranslated region or within the open reading frame of the toxin hamper its translation by stabilizing stem-loop structures that sequester the Shine-Dalgarno sequence. We propose that these short hairpins correspond to metastable structures that are transiently formed during transcription to avoid premature toxin expression. This work uncovers the co-transcriptional inhibition of translation as an additional layer of TA regulation in bacteria.