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bioRxiv · 10.64898/2026.11.10.765585

A ribosome-dependent small-ORF switch controls flagellar gene expression and virulence

Lastovka, F.·Bryant, O. J.·Meggers, D.·Alexeeva, E.·Knorr, M.·Narberhaus, F.·Chung, B. Y.
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Abstract

RNA structures are active regulators of bacterial translation. Here, we identified a naturally occurring translation-enhancing small open reading frame (tesORF) that controls the expression of the flagellar operon fliFGHIJK in Salmonella enterica and other motile Enterobacterales. Nucleotide-resolution ribosome profiling revealed this previously unannotated 54-nucleotide ORF immediately upstream of fliF. Genetic, transcriptomic, and biochemical analyses support a model in which tesORF translation counteracts an inhibitory RNA structure, exposing the fliF ribosome-binding site and promoting translation initiation independently of the encoded peptide sequence. Disruption of tesORF translation reduced expression of the downstream operon and impaired motility and virulence-associated phenotypes in Escherichia coli, Salmonella, and Yersinia. Together, our findings reveal how translation of a conserved small ORF regulates an entire flagellar operon through RNA structural remodelling, with consequences expending to the wider flagellar regulon, linking RNA structural dynamics to bacterial motility and virulence.

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Lastovka, F., Bryant, O. J., Meggers, D., Alexeeva, E., Knorr, M., Narberhaus, F., Chung, B. Y.. 2026-11-11. A ribosome-dependent small-ORF switch controls flagellar gene expression and virulence. https://doi.org/10.64898/2026.11.10.765585

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