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MqsA DNA-binding transcriptional repressor

Synonyms: MqsA
Summary:
The antitoxin MqsA belongs to the toxin-antitoxin system MqsR-MqsA, which controls biofilm formation and triggers programmed cell death in E. coli [4]. mqsR is cotranscribed with the downstream gene mqsA, and their respective open reading frames are separated by 1 bp. Contrary to what was reported by Yamaguchi et al. [4], Fraikin et al. reported that MqsA does not regulate biofilm formation and is not a response to stress [3]. Single-cell quantitative measurements show the existence of two cell populations with high or low levels of the MqsA antitoxin that respond differently to environmental stresses [7]. The toxin MqsR functions as an mRNA interferase, that is, it possesses endoribonuclease activity and cleaves mRNA at the specific sequence GCU, 5' or 3' of the G. Elevated levels of free MqsR result in programmed cell death due to the degradation of mRNA and concomitant inhibition of protein synthesis [4]. The antitoxin MqsA has two functions.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) References
MqsA Functional   nd nd nd
Evolutionary Family: CxxCG_CxxCG_HTH, MqsR
TFBs length: 15
TFBs symmetry: inverted-repeat
Connectivity class: Local Regulator
Gene name: mqsA
  Genome position: 3167851-3168246
  Length: 396 bp / 131 aa
Operon name: mqsRA
TU(s) encoding the TF:
Transcription unit        Promoter
mqsA
mqsAp1
mqsA
mqsAp2
mqsRA
mqsRp1
mqsRA
mqsRp2


Regulon       
Regulated gene(s) csgD, csgE, csgF, csgG, cspD, mqsA, mqsR, rpoS
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
Transcription related (1)
activator (1)
repressor (1)
Accessory Factors Involved in Transport (1)
fimbri, pili (1)
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Regulated operon(s) csgDEFG, cspD, mqsRA, nlpD-rpoS
First gene in the operon(s) csgD, cspD, mqsR, rpoS
Simple and complex regulons ArcA,CRP,Fur,GadX,MqsA,ppGpp
BasR,BolA,BtsR,CRP,CpxR,Cra,CsgD,FliZ,H-NS,IHF,MlrA,MqsA,OmpR,RcdA,RcsAB,RstA,ppGpp
BasR,BtsR,CRP,CpxR,Cra,CsgD,FliZ,H-NS,IHF,MlrA,MqsA,OmpR,RcdA,RcsAB,RstA
CRP,H-NS,MqsA,ppGpp
MqsA
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[MqsA,-](5)


Transcription factor regulation    


Transcription factor binding sites (TFBSs) arrangements
      

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence LeftPos RightPos Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) References
  MqsA repressor csgDp1 Sigma70 -83.5 -231.5 csgD, csgE, csgF, csgG
aaacttaataAAACCTTAAGGTTAacattttaat
 1103421 1103434 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [1], [1]
  MqsA repressor csgDp3 Sigma38 -83.5 -231.5 csgD, csgE, csgF, csgG
aaacttaataAAACCTTAAGGTTAacattttaat
 1103421 1103434 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [1], [1]
  MqsA repressor cspDp Sigma70 -132.5 -218.5 cspD
atgatagataACTATCATCTATCGTTGGCatcagcgaca
 922800 922818 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [2], [2]
  MqsA repressor cspDp Sigma70 101.5 15.5 cspD
gaagcatggaAAAGGGTACTGTTAAGTGGttcaacaatg
 922567 922585 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [2], [2]
  MqsA repressor mqsRp1 Sigma70 42.0 -68.0 mqsR, mqsA
tacatctaacTAACCTTTTAGGTGCtttttcattg
 3168605 3168619 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [3], [4], [4], [5]
  MqsA repressor mqsRp1 Sigma70 74.0 -36.0 mqsR, mqsA
ttgctgtaatTAACCTTTTAGGTTAtaactaaagt
 3168573 3168587 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [3], [4], [4], [5]
  MqsA repressor rpoSp Sigma70 -147.0 -714.0 rpoS
gaacgttggtCAGACCTTGCAGGTGGgtaatgcttc
 2868258 2868273 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [6], [6]


Alignment and PSSM for MqsA TFBSs    

Aligned TFBS of MqsA   
  Sequence
  AAGCACCTAAAAGGTTAGTTA
  TATAACCTAAAAGGTTAATTA
  TCAGACCTTGCAGGTGGGTAA
  TAAAACCTTAAGGTTAACATT
  AACCACTTAACAGTACCCTTT
  GCCAACGATAGATGATAGTTA

Position weight matrix (PWM). MqsA matrix-quality result    
A	2	4	2	3	6	0	0	1	3	5	3	5	0	0	2	1	4	1	1	1	4
C	0	2	2	2	0	6	4	0	0	0	2	0	0	0	0	1	1	2	0	0	0
G	1	0	1	1	0	0	1	0	0	1	1	1	5	4	0	1	1	3	0	0	0
T	3	0	1	0	0	0	1	5	3	0	0	0	1	2	4	3	0	0	5	5	2

Consensus    
;	consensus.strict             	tacaACCtaaaaGGttagtta
;	consensus.strict.rc          	TAACTAACCTTTTAGGTTGTA
;	consensus.IUPAC              	wmmmACCtwamaGKwtasttw
;	consensus.IUPAC.rc           	WAASTAWMCTKTWAGGTKKKW
;	consensus.regexp             	[at][ac][ac][ac]ACCt[at]a[ac]aG[GT][at]ta[cg]tt[at]
;	consensus.regexp.rc          	[AT]AA[CG]TA[AT][AC]CT[GT]T[AT]AGGT[GT][GT][GT][AT]

PWM logo   


 


Evolutionary conservation of regulatory elements    
     Note: Evolutionary conservation of regulatory interactions and promoters is limited to gammaproteobacteria.
TF-target gene evolutionary conservation
Promoter-target gene evolutionary conservation


Evidence    

 [EXP-IEP-GENE-EXPRESSION-ANALYSIS] Gene expression analysis

 [COMP-HINF-SIMILAR-TO-CONSENSUS] A person inferred or reviewed a computer inference of sequence function based on similarity to a consensus sequence.

 [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] Binding of purified proteins

 [COMP-HINF] Inferred by a human based on computational evidence

 [EXP-DAP-SEQ] high throughput DNA Affinity Purification (DAP) Sequencing

 [EXP-IMP-SITE-MUTATION] Site mutation


Reference(s)    

 [1] Soo VW., Wood TK., 2013, Antitoxin MqsA represses curli formation through the master biofilm regulator CsgD., Sci Rep 3:3186

 [2] Kim Y., Wang X., Zhang XS., Grigoriu S., Page R., Peti W., Wood TK., 2010, Escherichia coli toxin/antitoxin pair MqsR/MqsA regulate toxin CspD., Environ Microbiol 12(5):1105-21

 [3] Fraikin N., Rousseau CJ., Goeders N., Van Melderen L., 2019, Reassessing the Role of the Type II MqsRA Toxin-Antitoxin System in Stress Response and Biofilm Formation: mqsA Is Transcriptionally Uncoupled from mqsR., mBio 10(6)

 [4] Yamaguchi Y., Park JH., Inouye M., 2009, MqsR, a crucial regulator for quorum sensing and biofilm formation, is a GCU-specific mRNA interferase in Escherichia coli., J Biol Chem 284(42):28746-53

 [5] Baumgart LA, Lee JE, Salamov A, Dilworth DJ, Na H, Mingay M, Blow MJ, Zhang Y, Yoshinaga Y, Daum CG, O'Malley RC, 2021, Persistence and plasticity in bacterial gene regulation., Nat Methods, 18(12):1499 10.1038/s41592-021-01312-2

 [6] Wang X., Kim Y., Hong SH., Ma Q., Brown BL., Pu M., Tarone AM., Benedik MJ., Peti W., Page R., Wood TK., 2011, Antitoxin MqsA helps mediate the bacterial general stress response., Nat Chem Biol 7(6):359-66

 [7] Wu L, Zhang M, Song Y, Deng M, He S, Su L, Chen Y, Wood TK, Yan X, 2019, Deciphering the Antitoxin-Regulated Bacterial Stress Response via Single-Cell Analysis., ACS Chem Biol, 14(12):2859 10.1021/acschembio.9b00721

 [8] Brown BL, Lord DM, Grigoriu S, Peti W, Page R, 2013, The Escherichia coli toxin MqsR destabilizes the transcriptional repression complex formed between the antitoxin MqsA and the mqsRA operon promoter., J Biol Chem, 288(2):1286 10.1074/jbc.M112.421008

 [9] Papadopoulos E, Billeter M, Gräslund A, Vlamis-Gardikas A, 2007, Assignment of (1)H, (13)C, and (15)N resonances of YgiT, a putative DNA interacting protein from E. coli, containing one HTH and two CxxC motifs., Biomol NMR Assign, 1(2):217 10.1007/s12104-007-9060-x

 [10] Papadopoulos E, Collet JF, Vukojevi? V, Billeter M, Holmgren A, Gräslund A, Vlamis-Gardikas A, 2012, Solution structure and biophysical properties of MqsA, a Zn-containing antitoxin from Escherichia coli., Biochim Biophys Acta, 1824(12):1401 10.1016/j.bbapap.2012.06.016

 [11] Brown BL, Grigoriu S, Kim Y, Arruda JM, Davenport A, Wood TK, Peti W, Page R, 2009, Three dimensional structure of the MqsR:MqsA complex: a novel TA pair comprised of a toxin homologous to RelE and an antitoxin with unique properties., PLoS Pathog, 5(12):e1000706 10.1371/journal.ppat.1000706

 [12] Brown BL, Wood TK, Peti W, Page R, 2011, Structure of the Escherichia coli antitoxin MqsA (YgiT/b3021) bound to its gene promoter reveals extensive domain rearrangements and the specificity of transcriptional regulation., J Biol Chem, 286(3):2285 10.1074/jbc.M110.172643

 [13] Inouye M, 2006, The discovery of mRNA interferases: implication in bacterial physiology and application to biotechnology., J Cell Physiol, 209(3):670 10.1002/jcp.20801

 [14] Yamaguchi Y, Inouye M, 2009, mRNA interferases, sequence-specific endoribonucleases from the toxin-antitoxin systems., Prog Mol Biol Transl Sci, 85(None):467 10.1016/S0079-6603(08)00812-X

 [15] Yamaguchi Y, Park JH, Inouye M, 2011, Toxin-antitoxin systems in bacteria and archaea., Annu Rev Genet, 45(None):61 10.1146/annurev-genet-110410-132412


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