Condensation of the RNA chaperone Hfq is coupled to inhibition of carbon assimilation and contributes to the stabilisation of regulatory RNAs in nitrogen starved Escherichia coli

Abstract

Ribonucleoprotein-condensates are membraneless compartments that concentrate RNA-binding proteins and RNA and play key roles in cellular adaptation across both eukaryotes and bacteria. While the biological roles of ribonucleoprotein-condensates are better understood in eukaryotic systems, the knowledge of metabolic processes that govern their formation and their contribution to stress adaptation remains at a nascent stage in bacterial RNA biology. Hfq is an RNA-chaperone conserved in many bacteria that undergoes condensation in response to diverse stresses. Using nitrogen (N) starvation in Escherichia coli as a model stress condition, we show that Hfq condensation occurs independently of any extracellular cues, cytoplasmic shrinkage that cells undergo during N starvation or the canonical NtrBC-dependent adaptive response to N starvation. However, we demonstrate that Hfq condensation is coupled to the inhibition of carbon assimilation in N-starved E. coli. Further, by comparing the transcriptomes of wild-type bacteria and bacteria unable to form Hfq-condensates, we reveal that Hfq-condensates contribute to the stabilisation of Hfq-associated non-coding regulatory RNAs. We propose that coordination of carbon and N metabolism during N starvation, critical for metabolic adaptation, is accompanied by preservation of non-coding regulatory RNAs via Hfq condensation.