RelA protein stimulates the activity of RyhB small RNA by acting on RNA-binding protein Hfq

Liron Argaman, Maya Elgrably-Weiss, Tal Hershko, Jörg Vogel, Shoshy Altuvia*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


The conserved RNA-binding protein Hfq and its associated small regulatory RNAs (sRNAs) are increasingly recognized as the players of a large network of posttranscriptional control of gene expression in Gram-negative bacteria. The role of Hfq in this network is to facilitate base pairing between sRNAs and their trans-encoded target mRNAs. Although the number of known sRNA-mRNA interactions has grown steadily, cellular factors that influence Hfq, the mediator of these interactions, have remained unknown. We report that RelA, a protein long known as the central regulator of the bacterial-stringent response, acts on Hfq and thereby affects the physiological activity of RyhB sRNA as a regulator of iron homeostasis. RyhB requires RelA in vivo to arrest growth during iron depletion and to down-regulate a subset of its target mRNAs (fdoG, nuoA, and sodA), whereas the sodB and sdhC targets are barely affected by RelA. In vitro studies with recombinant proteins show that RelA enhances multimerization of Hfq monomers and stimulates Hfq binding of RyhB and other sRNAs. Hfq from polysomes extracted from wild-type cells binds RyhB in vitro, whereas Hfq from polysomes of a relA mutant strain shows no binding. We propose that, by increasing the level of the hexameric form of Hfq, RelA enables binding of RNAs whose affinity for Hfq is low. Our results suggest that, under specific conditions and/or environments, Hfq concentrations are limiting for RNA binding, which thereby provides an opportunity for cellular proteins such as RelA to impact sRNA-mediated responses by modulating the activity of Hfq.

Original languageAmerican English
Pages (from-to)4621-4626
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number12
StatePublished - 20 Mar 2012


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