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

Authors

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.

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.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 13 Aug 2026.

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