A small RNA guides a post-transcriptional regulatory protein to its target

Faigenbaum-Romm, R.; Aroeti, L.; Elbaz, N.; Fisher, S.; Altuvia, Y.; Argaman, L.; Barsheshet, M.; Ravins, M.; Katsowich, N.; Xiong, Y.; Ben-Yehuda, S.; Margalit, H.; Rosenshine, I.

doi:10.64898/2026.08.12.744399

bioRxiv · 10.64898/2026.08.12.744399

A small RNA guides a post-transcriptional regulatory protein to its target

Faigenbaum-Romm, R.·Aroeti, L.·Elbaz, N.·Fisher, S.·Altuvia, Y.·Argaman, L.·Barsheshet, M.·Ravins, M.·Katsowich, N.·Xiong, Y.·Ben-Yehuda, S.·Margalit, H.·Rosenshine, I.

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Abstract

RNA-binding proteins are central to post-transcriptional regulation and are generally thought to recognize their target RNAs through direct binding. Here, we uncover a previously unrecognized mechanism in which a small RNA (sRNA) guides a protein regulator to specific target mRNAs, enabling programmable post-transcriptional control. By mapping in pathogenic Escherichia coli the RNA interactome of CsrA, a global post-transcriptional regulator, we identify ~800 ternary complexes in which CsrA simultaneously binds an sRNA and an mRNA. Focusing on one class of these complexes, we show that PasE, a newly discovered sRNA, directs CsrA to virulence-associated mRNAs that are otherwise not targeted by CsrA, resulting in their repression. Altering the PasE seed sequence redirects CsrA to selected mRNAs, establishing a modular RNA-guided platform for gene regulation. Together, our findings reveal a new and likely widespread mechanism of bacterial post-transcriptional regulation and provide a framework for a new type of RNA-based synthetic regulation.

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Faigenbaum-Romm, R., Aroeti, L., Elbaz, N., Fisher, S., Altuvia, Y., Argaman, L., Barsheshet, M., Ravins, M., Katsowich, N., Xiong, Y., Ben-Yehuda, S., Margalit, H., Rosenshine, I.. 2026-08-12. A small RNA guides a post-transcriptional regulatory protein to its target. https://doi.org/10.64898/2026.08.12.744399

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