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.