FasX small RNA

Last updated

In molecular biology, the FasX small RNA (fibronectin/fibrinogen-binding/haemolytic-activity/streptokinase-regulator-X) is a non-coding small RNA (sRNA) produced by all group A Streptococcus . [1] FasX has also been found in species of group D and group G Streptococcus . FasX regulates expression of secreted virulence factor streptokinase (SKA), encoded by the ska gene. FasX base pairs to the 5' end of the ska mRNA, increasing the stability of the mRNA, resulting in elevated levels of streptokinase expression. [2] FasX negatively regulates the expression of pili and fibronectin-binding proteins on the bacterial cell surface. It binds to the 5' untranslated region of genes in the FCT-region in a serotype-specific manner, reducing the stability of and inhibiting translation of the pilus biosynthesis operon mRNA by occluding the ribosome-binding site through a simple Watson-Crick base-pairing mechanism. [3] [4] [5]

Contents

See also

Related Research Articles

The gene rpoS encodes the sigma factor sigma-38, a 37.8 kD protein in Escherichia coli. Sigma factors are proteins that regulate transcription in bacteria. Sigma factors can be activated in response to different environmental conditions. rpoS is transcribed in late exponential phase, and RpoS is the primary regulator of stationary phase genes. RpoS is a central regulator of the general stress response and operates in both a retroactive and a proactive manner: it not only allows the cell to survive environmental challenges, but it also prepares the cell for subsequent stresses (cross-protection). The transcriptional regulator CsgD is central to biofilm formation, controlling the expression of the curli structural and export proteins, and the diguanylate cyclase, adrA, which indirectly activates cellulose production. The rpoS gene most likely originated in the gammaproteobacteria.

RNAIII is a stable 514 nt regulatory RNA transcribed by the P3 promoter of the Staphylococcus aureus quorum-sensing agr system ). It is the major effector of the agr regulon, which controls the expression of many S. aureus genes encoding exoproteins and cell wall associated proteins plus others encoding regulatory proteins The RNAIII transcript also encodes the 26 amino acid δ-haemolysin peptide (Hld). RNAIII contains many stem loops, most of which match the Shine-Dalgarno sequence involved in translation initiation of the regulated genes. Some of these interactions are inhibitory, others stimulatory; among the former is the regulatory protein Rot. In vitro, RNAIII is expressed post exponentially, inhibiting translation of the surface proteins, notably protein A, while stimulating that of the exoproteins, many of which are tissue-degrading enzymes or cytolysins. Among the latter is the important virulence factor, α-hemolysin (Hla), whose translation RNAIII activates by preventing the formation of an inhibitory foldback loop in the hla mRNA leader.

<span class="mw-page-title-main">RsmY RNA family</span>

The rsmY RNA family is a set of related non-coding RNA genes, that like RsmZ, is regulated by the GacS/GacA signal transduction system in the plant-beneficial soil bacterium and biocontrol model organism Pseudomonas fluorescens CHA0. GacA/GacS target genes are translationally repressed by the small RNA binding protein RsmA. RsmY and RsmZ RNAs bind RsmA to relieve this repression and so enhance secondary metabolism and biocontrol traits.

<span class="mw-page-title-main">MicA RNA</span>

The MicA RNA is a small non-coding RNA that was discovered in E. coli during a large scale screen. Expression of SraD is highly abundant in stationary phase, but low levels could be detected in exponentially growing cells as well.

<span class="mw-page-title-main">ArcZ RNA</span>

In molecular biology the ArcZ RNA is a small non-coding RNA (ncRNA). It is the functional product of a gene which is not translated into protein. ArcZ is an Hfq binding RNA that functions as an antisense regulator of a number of protein coding genes.

<span class="mw-page-title-main">Hfq protein</span>

The Hfq protein encoded by the hfq gene was discovered in 1968 as an Escherichia coli host factor that was essential for replication of the bacteriophage Qβ. It is now clear that Hfq is an abundant bacterial RNA binding protein which has many important physiological roles that are usually mediated by interacting with Hfq binding sRNA.

<span class="mw-page-title-main">Hfq binding sRNA</span>

An Hfq binding sRNA is an sRNA that binds the bacterial RNA binding protein called Hfq. A number of bacterial small RNAs which have been shown to bind to Hfq have been characterised . Many of these RNAs share a similar structure composed of three stem-loops. Several studies have expanded this list, and experimentally validated a total of 64 Hfq binding sRNA in Salmonella Typhimurium. A transcriptome wide study on Hfq binding sites in Salmonella mapped 126 Hfq binding sites within sRNAs. Genomic SELEX has been used to show that Hfq binding RNAs are enriched in the sequence motif 5′-AAYAAYAA-3′. Genome-wide study identified 40 candidate Hfq-dependent sRNAs in plant pathogen Erwinia amylovora. 12 of them were confirmed by Northern blot.

<span class="mw-page-title-main">Sortase</span> Group of prokaryotic enzymes

Sortase refers to a group of prokaryotic enzymes that modify surface proteins by recognizing and cleaving a carboxyl-terminal sorting signal. For most substrates of sortase enzymes, the recognition signal consists of the motif LPXTG (Leu-Pro-any-Thr-Gly), then a highly hydrophobic transmembrane sequence, followed by a cluster of basic residues such as arginine. Cleavage occurs between the Thr and Gly, with transient attachment through the Thr residue to the active site Cys residue, followed by transpeptidation that attaches the protein covalently to cell wall components. Sortases occur in almost all Gram-positive bacteria and the occasional Gram-negative bacterium or Archaea, where cell wall LPXTG-mediated decoration has not been reported. Although sortase A, the "housekeeping" sortase, typically acts on many protein targets, other forms of sortase recognize variant forms of the cleavage motif, or catalyze the assembly of pilins into pili.

<span class="mw-page-title-main">Asd RNA motif</span> Structure in lactic-acid bacterium RNA

The asd RNA motif is a conserved RNA structure found in certain lactic acid bacteria. The asd motif was detected by bioinformatics and an individual asd RNA in Streptococcus pyogenes was detected by microarray and northern hybridization experiments as a 170-nucleotide molecule called "SR914400". The transcription start site determined for SR914400 corresponds to the 5′-end of the molecule shown in the consensus diagram.

Bacterial small RNAs (bsRNA) are small RNAs produced by bacteria; they are 50- to 500-nucleotide non-coding RNA molecules, highly structured and containing several stem-loops. Numerous sRNAs have been identified using both computational analysis and laboratory-based techniques such as Northern blotting, microarrays and RNA-Seq in a number of bacterial species including Escherichia coli, the model pathogen Salmonella, the nitrogen-fixing alphaproteobacterium Sinorhizobium meliloti, marine cyanobacteria, Francisella tularensis, Streptococcus pyogenes, the pathogen Staphylococcus aureus, and the plant pathogen Xanthomonas oryzae pathovar oryzae. Bacterial sRNAs affect how genes are expressed within bacterial cells via interaction with mRNA or protein, and thus can affect a variety of bacterial functions like metabolism, virulence, environmental stress response, and structure.

<span class="mw-page-title-main">Streptococcal pyrogenic exotoxin</span>

Streptococcal pyrogenic exotoxins also known as erythrogenic toxins, are exotoxins secreted by strains of the bacterial species Streptococcus pyogenes. SpeA and speC are superantigens, which induce inflammation by nonspecifically activating T cells and stimulating the production of inflammatory cytokines. SpeB, the most abundant streptococcal extracellular protein, is a cysteine protease. Pyrogenic exotoxins are implicated as the causative agent of scarlet fever and streptococcal toxic shock syndrome. There is no consensus on the exact number of pyrogenic exotoxins. Serotypes A-C are the most extensively studied and recognized by all sources, but others note up to thirteen distinct types, categorizing speF through speM as additional superantigens. Erythrogenic toxins are known to damage the plasma membranes of blood capillaries under the skin and produce a red skin rash. Past studies have shown that multiple variants of erythrogenic toxins may be produced, depending on the strain of S. pyogenes in question. Some strains may not produce a detectable toxin at all. Bacteriophage T12 infection of S. pyogenes enables the production of speA, and increases virulence.

Mga is a DNA-binding protein that activates the expression of several important virulence genes in Streptococcus pyogenes in response to changing environmental conditions. The family also contains VirR like proteins which match only at the C-terminus.

<span class="mw-page-title-main">RivX sRNA</span>

RivX sRNA is a non-coding RNA molecule involved in the interface between two key regulators of virulence in the human pathogen Streptococcus pyogenes : the CovR/S system and Mga regulator. This RNA, along with its downstream protein-coding gene RivR, are the first discovered links between these two important regulation networks. An extra protein linking the two pathways, TrxR, was described a year later. The adjoining of these two pathways could allow a consistently high virulence of S. pyogenes despite a variety of environmental conditions.

In molecular biology, cia-dependent small RNAs (csRNAs) are small RNAs produced by Streptococci. These RNAs are part of the regulon of the CiaRH two-component regulatory system. Two of these RNAs, csRNA4 and csRNA5, have been shown to affect stationary-phase autolysis.

In molecular biology, Streptococcus sRNAs are small RNAs produced by species of Streptococcus bacteria. Several screens have identified numerous sRNAs in different species and strains of Streptococcus including S. pneumoniae, S. pyogenes, S. agalactiae and S.mutans. The function of most of these is currently unknown, however a few have been characterised including FasX small RNA. Many sRNAs have roles in pathogenesis.

In molecular biology, Vibrio cholerae ToxT activated RNAs are small RNAs which are produced by the bacterium Vibrio cholerae. They are regulated by the transcriptional activator ToxT and may play a role in V. cholerae virulence. Two ToxT activated RNAs have been described: TarA and TarB.

The gene rpoN encodes the sigma factor sigma-54, a protein in Escherichia coli and other species of bacteria. RpoN antagonizes RpoS sigma factors.

Bacterial small RNAs (sRNA) are an important class of regulatory molecules in bacteria such as Brucella. They are often bound to the chaperone protein Hfq, which allows them to interact with mRNA(s). In Brucella suis 1330 RNA sequencing identified a novel list of 33 sRNAs and 62 Hfq-associated mRNAs. In Brucella melitensis eight novel sRNA genes were identified using bioinformatic and experimental approach. One of them BSR0602 was found to modulate the intracellular survival of B. melitensis. In another large-scale deep sequencing study 1321 sRNAs were identified in B. melitensis. BSR0441 sRNA was further investigated in this study and shown to play role in the intracellular survival. sRNA BM-sr0117 from Brucella melitensis was identified and shown to be bound to and cleaved by Bm-RNase III. AbcR and AbcR2 were studied B. abortus. Seven novel sRNAs were validated and their interaction with a putative target sequence was verified in B. abortus.

RopB transcriptional regulator, also known as RopB/Rgg transcriptional regulator is a transcriptional regulator protein that regulates expression of the extracellularly secreted cysteine protease streptococcal pyrogenic exotoxin B (speB) [See Also: erythrogenic toxins] which is an important virulence factor of Streptococcus pyogenes and is responsible for the dissemination of a host of infectious diseases including strep throat, impetigo, streptococcal toxic shock syndrome, necrotizing fasciitis, and scarlet fever. Functional studies suggest that the ropB multigene regulon is responsible for not only global regulation of virulence but also a wide range of functions from stress response, metabolic function, and two-component signaling. Structural studies implicate ropB's regulatory action being reliant on a complex interaction involving quorum sensing with the leaderless peptide signal speB-inducing peptide (SIP) acting in conjunction with a pH sensitive histidine switch.

References

  1. Kreikemeyer, B; Boyle, MD; Buttaro, BA; Heinemann, M; Podbielski, A (Jan 2001). "Group A streptococcal growth phase-associated virulence factor regulation by a novel operon (Fas) with homologies to two-component-type regulators requires a small RNA molecule". Molecular Microbiology. 39 (2): 392–406. doi: 10.1046/j.1365-2958.2001.02226.x . PMID   11136460. S2CID   20242213.
  2. Ramirez-Peña, E; Treviño, J; Liu, Z; Perez, N; Sumby, P (Dec 2010). "The group A Streptococcus small regulatory RNA FasX enhances streptokinase activity by increasing the stability of the ska mRNA transcript". Molecular Microbiology. 78 (6): 1332–1347. doi:10.1111/j.1365-2958.2010.07427.x. PMC   3071709 . PMID   21143309.
  3. Liu, Z; Treviño, J; Ramirez-Peña, E; Sumby, P (Oct 2012). "The small regulatory RNA FasX controls pilus expression and adherence in the human bacterial pathogen group A Streptococcus". Molecular Microbiology. 86 (1): 140–154. doi:10.1111/j.1365-2958.2012.08178.x. PMC   3456998 . PMID   22882718.
  4. Danger, JL; Cao, TN; Cao, TH; Sarkar, P; Treviño, J; Pflughoeft, KJ; Sumby, P (April 2015). "The small regulatory RNA FasX enhances group A Streptococcus virulence and inhibits pilus expression via serotype-specific targets". Molecular Microbiology. 96 (2): 249–262. doi:10.1111/mmi.12935. PMC   4390479 . PMID   25586884.
  5. Danger, JL; Makthal, N; Kumaraswami, M; Sumby, P (1 December 2015). "The FasX Small Regulatory RNA Negatively Regulates the Expression of Two Fibronectin-Binding Proteins in Group A Streptococcus". Journal of Bacteriology. 197 (23): 3720–3730. doi:10.1128/jb.00530-15. PMC   4626899 . PMID   26391206.

Further reading