The Multiple Regulatory Relationship Between RNA-Chaperone Hfq and the Second Messenger c-di-GMP

Abstract

RNA chaperone protein Hfq is an important post-transcriptional regulator in bacteria, while c-di-GMP is a second messenger signaling molecule widely distributed in bacteria. Both factors have been found to play key roles in post-transcriptional regulation and signal transduction pathways, respectively. Intriguingly, the two factors show some common aspects in the regulation of certain physiological functions such as bacterial motility, biofilm formation, pathogenicity and so on. Therefore, there may be regulatory relationship between Hfq and c-di-GMP. For example, Hfq can directly regulate the activity of c-di-GMP metabolic enzymes or alter the c-di-GMP level through other systems, while c-di-GMP can indirectly enhance or inhibit the hfq gene expression through intermediate factors. In this article, after briefly introducing the Hfq and c-di-GMP regulatory systems, we will focus on the direct and indirect regulation reported between Hfq and c-di-GMP, aiming to compare and link the two regulatory systems to further study the complicated physiological and metabolic systems of bacteria, and to lay a solid foundation for drawing a more complete global regulatory network.

The enhanced expression of genes encoding diguanylate cyclases under cold stress contributes to the adhesion and biofilm formation of Shewanella putrefaciens WS13

“…Briefly, 1 mL of diluted culture was added into 48-well polystyrene microtiter plates; then, the plates were covered by plastic to avoid evaporative loss. According to bacterial growth curves, after certain cultivation times (6,12,18,24,30,36, and 42 h under 30 • C; 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, and 264 h under 4 • C), biofilms in wells were carefully cleaned three times with 1 mL of 0.01 M sterile phosphate-buffered saline (PBS, pH 7.0) to remove unattached cells. After being dried for 25 min under 60 • C, biofilms were stained with 1 mL of 0.2% (w/v) crystal violet (Sangon Biotech, Co., Ltd., Shanghai, China) for 15 min, then washed and dried as described above.…”

“…To adapt to the complex and changeable environment, there are various signal transduction systems in bacterial cells to ensure the survival of bacteria, such as cyclic diguanylic acid (c-di-GMP) ( 18 ) and two-component systems ( 19 ). As the ubiquitous second messenger in bacteria, c-di-GMP modulates diverse biological phenotypes in bacteria such as virulence, flagellar motility, biofilm formation ( 17 ), and bacterial colonization ( 20 ).…”

The RNA Chaperone Protein Hfq Regulates the Characteristic Sporulation and Insecticidal Activity of Bacillus thuringiensis

“…Meanwhile, Hfq can also directly bind to certain mRNAs to control their translation, and ultimately affect the expression of specific proteins. For example, Hfq can affect bacterial intracellular c-di-GMP concentration and regulate bacterial biofilm formation through post-transcriptional repression of mRNA translation of the diguanylate cyclase-encoding gene hms T ( Ellis et al, 2015 ; Chen and Gottesman, 2017 ; Fu et al, 2021 ). In addition, Hfq can also promote the base pairing of sRNA with its target mRNA, thereby regulating the expression level of target genes ( Pfeiffer et al, 2009 ; Hämmerle et al, 2012 ), affecting bacterial growth and environmental adaptability ( Vogt and Raivio, 2014 ), abrogating carbon catabolite repression ( Sonnleitner and Bläsi, 2014 ), and altering bacterial virulence to the host ( Dos Santos et al, 2019 ).…”

“…Taken together, the diversity of Hfq regulatory mechanisms suggests that Hfq is indeed a flexible RNA mediator that can compete with hundreds of sRNA molecules and thousands of mRNA sequences for binding to affect various bacterial physiological activities mediated by these RNAs. Therefore, Hfq is a bona fide global post-transcriptional regulator in bacteria ( Zhang et al, 2003 ; Fu et al, 2021 ).…”

Identification of small RNAs associated with RNA chaperone Hfq reveals a new stress response regulator in Actinobacillus pleuropneumoniae

“…The Hfq protein forms a homo-hexameric ring and it is involved in several essential processes, such as rRNA processing, ribosome biogenesis, tRNA maturation, control of mRNA translation, DNA compaction, and activity of c-di-GMP metabolic enzymes ( Kavita et al, 2018 ; dos Santos et al, 2019 ; Fu et al, 2021 ). However, its most prominent activity involves dynamically binding to small non-coding RNA molecules (sRNAs; Quendera et al, 2020 ).…”