The power duo: how the interplay between nucleoid-associated proteins and small non-coding RNAs orchestrates the cellular regulatory symphony

In bacteria, the regulation of gene expression involves complex networks that integrate both transcriptional and post-transcriptional mechanisms. At the transcriptional level, nucleoid-associated proteins (NAPs) such as H-NS, HU, Lrp, IHF, Fis and Hfq are key players as they not only compact bacterial DNA, but also regulate transcription. Small non-coding RNAs (sRNAs), on the other hand, affect bacterial gene expression post-transcriptionally by base pairing with the target mRNA. Interestingly, certain NAPs also influence the function of sRNAs and, conversely, sRNAs themselves can modulate the activity of NAPs, creating a complex bidirectional regulatory network. Here, we summarise the current knowledge of the major NAPs, focusing on the specific role of Hfq. Examples of the regulation of NAPs by sRNAs, the regulation of sRNAs by NAPs and the role of sRNAs in nucleoid structuring are also discussed. This review focuses on the cross-talk between NAPs and sRNAs in an attempt to understand how the interplay between cellular proteins and regulatory RNAs contributes to the fine-tuning regulation of bacterial gene expression.