7) Concluding remarks
The regulation of gene expression is a complex process involving different levels that may interact with each other. This review discusses the interplay between nucleoid-structuring proteins, which also regulate transcription, and RNAs, which are involved in post-transcriptional regulation. It is highlighted that sRNA can be regulated by several NAPs and, conversely, one NAP can be the target of several sRNAs (Figure 2 ). Therefore, these regulatory molecules, either sRNAs or NAPs, could form hubs in regulatory networks. For example, DsrA regulates H-NS at the post-transcriptional level and binds to lrp mRNA. In addition, the HU protein also binds DsrA, suggesting that this sRNA may link these three NAPs. This raises questions about the function of these cross-talks. One hypothesis is that a sRNA could indirectly modify the chromosome conformation by regulating NAPs. This is partially illustrated by the result for Hfq, which compacts DNA without altering its topology, but the disruption of the hfq gene affects plasmid supercoiling in vivo (Cechet al. , 2016), suggesting an indirect effect of Hfq on DNA topology through its RNA chaperone function on sRNA (Figure 2 ). The hypothesis is that an unknown sRNA post-transcriptionally regulates NAPs, which in turn affects DNA supercoiling (Malabirade et al. , 2018b). Taking this a step further, such regulation could promote the activity of one NAP with its DNA binding specificity rather than another. Regulation of NAPs by sRNAs may also be specific to certain environmental growth conditions, promoting a switch to ensure an appropriate level of NAPs. It is also worth considering the physiological impact of sRNA regulation of highly abundant proteins such as NAPs. Although some NAPs are regulated by several sRNAs, it is possible that their regulation is additive.
Cross-talk between NAPs and sRNAs is also highlighted by the protein Hfq, which functions both as an RNA chaperone and as a NAP. Although the two functions of Hfq have been studied separately, they may be connected. Questions about how, when and where this connection occurs remain to be answered.
In addition to Hfq, other NAPs such as H-NS-like proteins, or HU have been shown to bind RNA. It is unclear whether this affinity has a physiological function. However, some sRNAs, known as nucleoid-associated ncRNAs, are directly involved in DNA compaction and the affinity of HU to these RNAs is directly involved in this phenomenon. Further research is needed to fully understand the role of sRNA in the chromosome structure. In conclusion, this review highlights the intricate interrelationship between NAPs, sRNAs, and chromosome structure in bacterial gene expression regulation and sheds new light on the potential to develop an interdisciplinary field that could overcome current barriers to understanding the global cellular regulatory network.