While transcriptional reprogramming is perhaps the most well understood form of controlling gene expression in response to nitrogen starvation in bacteria, how post-transcriptional regulation (PTR) of gene expression contributes to this adaptive response remains elusive. Small regulatory RNAs (sRNAs) are the major post-transcriptional regulators of gene expression in bacteria. They regulate gene expression by base pairing to target mRNAs, leading to enhanced translation or inhibition of translation and/or alteration of mRNA stability. To form productive interactions with target mRNAs, most sRNAs require an RNA chaperone. In many bacteria of diverse lineages, the RNA chaperone Hfq plays a central and integral role in the PTR of gene expression by stabilising sRNAs and promoting their interactions with cognate mRNAs. Comparative analysis of the transcriptomes of Escherichia coli at different stages of nitrogen starvation reveal that levels of sRNA vary throughout starvation. We used Hfq as a surrogate to study sRNA-mediated PTR of gene expression during sustained nitrogen starvation. Our results indicate that sRNAs-mediated PTR of gene expression plays a major role in the adaptive response to sustained nitrogen starvation. Intriguingly, using single-molecule PALM, we reveal that Hfq is involved in the formation of intracellular structures which functionally might resemble processing (P) bodies found in eukaryotic cells involved in mRNA turnover.

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