5.2) H-NS, bifunctional RNA and pervasive transcription
A recent study by Zhao et al., (2021) identified the hns mRNA as
a bifunctional RNA that down-regulates the expression of its
neighbouring gene, galU , thereby attenuating the motility ofS. enterica serovar Typhimurium. Bifunctional (or dual-function)
RNAs are defined as RNAs that can both be translated into proteins and
play regulatory roles. This group includes mRNAs that overlap with the
transcript of neighbouring genes transcribed from the complementary DNA
strand (Toledo-Arana and Lasa, 2020). Since these mRNA sequences are
complementary, they allow a regulatory mechanism using antisense RNAs.
In E. coli and S. enterica , the hns genes are
located on the opposite strand to the galU gene (Figure
3b ). The galU gene encodes a uridine
triphosphate-glucose-1-phosphate uridyltransferase, an enzyme that
facilitates the production of bacterial surface structures such as
lipopolysaccharide, extracellular polysaccharide and capsular
polysaccharide (Dean and Goldberg, 2002; Guo et al. , 2010; Zhaoet al. , 2021). Zhao et al., (2021) showed that the deletion ofgalU reduced the motility in S. Typhimurium, whereas
overexpression of hns mRNA inhibited motility and flagellar gene
expression in a galU -related manner. At the molecular level, thegalU mRNA was found to contain an extensive 3’-untranslated
region that overlaps with the hns mRNA. This long 3’ untranslated
region (UTR) is cleaved, resulting in the production of short RNA
fragments. The proposed mechanism involves the formation of an RNA
duplex between hns mRNA and the 3’UTR of galU , leading to
RNA cleavage and ultimately to galU -processed transcripts that
may be translationally inactive (Figure 3b ). Since bifunctional
RNAs occur in pairs and have two modes of regulation, it was also
suspected that the reverse regulation might also occur. Overexpression
of GalU-3’-UTR resulted in a decrease in hns mRNA and protein
levels compared to the control strain, leading to the assumption thatgalU mRNA could also act as an antisense RNA and regulatehns mRNA.