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MetaCyc Enzyme: mRNA interferase, toxin of the MqsR-MqsA toxin-antitoxin system

Gene: mqsR Accession Numbers: G7572 (MetaCyc), b3022, ECK3013

Synonyms: ygiU

Species: Escherichia coli K-12 substr. MG1655

Component of: MqsA-MqsR antitoxin/toxin complex (summary available)

Summary:
MqsR is a ribosome-independent mRNA interferase that inhibits protein synthesis by specifically cleaving mRNA at GCU sites [Yamaguchi09, ChristensenDals10]. The mRNA interferase activity is inhibited by interaction with MqsA [Yamaguchi09]. Expression of MqsR causes elongation of cells and reversible growth inhibition [Kasari10].

MqsR plays a role in controlling biofilm formation by inducing motility via the two-component regulatory system QseBC. MqsR links the AI-2 quorum sensing signal to biofilm formation [Gonzalez06a].

A crystal structure of the MqsR-MqsA complex has been solved, showing that two molecules of MqsR bind to an MqsA dimer [Brown09a]. Binding of MqsR destabilizes the MqsA-DNA complex [Brown13]. MqsR adopts an RNase fold similar to YoeB and RelE. Key residues required for toxicity of MqsR have been identified by site-directed mutagenesis [Brown09a]. Amino acid changes that increase the stability of MqsR also increase its toxicity and effect on persister cell formation [Hong12a].

Transcription of mqsR was found to be induced upon biofilm formation [Ren04], and deletion of mqsR decreases biofilm formation and abolishes motility [Gonzalez06a]. Contrasting with this result, it was also reported that deletion of mqsR increases biofilm formation [Kim10b]. It was later found that the strain background influences MqsR activity [Kasari10]. mqsR is more highly expressed in persister cells than non-persisters, and overexpression of mqsR leads to growth arrest and increased tolerance to certain antibiotics [Shah06, Zhang08a]. Co-induction of mqsA expression rescues cell growth [Yamaguchi09, ChristensenDals10]. However, the opposite effect was reported by [Zhang08a]. Deletion of mqsRA decreases persister cell formation [Kim10e], while overexpression of MqsR induces expression of CspD [Kim10b] and increases persister cell formation via both toxins Hha and CspD [Kim10e]. An mqsR deletion strain shows decreased levels of persister cells only when the inoculum is from aged cultures [Luidalepp11].

The Lon protease is required for activation of the mqsRA locus. Transcription is induced by chloramphenicol treatment, amino acid starvation induced by serine hydroxamate, isoleucine starvation, and glucose starvation [ChristensenDals10].

Based on sequence similarity, MqsR was predicted to be a cyanide hydratase [Reed03].

MqsR: "motility quorum-sensing regulator" [Gonzalez06a]

Reviews: [Yamaguchi11, Wang11e]

Map Position: [3,166,270 <- 3,166,566]

Molecular Weight of Polypeptide: 11.232 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0009925 , EchoBASE:EB2841 , EcoGene:EG13023 , EcoliWiki:b3022 , OU-Microarray:b3022 , PortEco:mqsR , PR:PRO_000023281 , Protein Model Portal:Q46865 , RefSeq:NP_417494 , RegulonDB:G7572 , SMR:Q46865 , String:511145.b3022 , UniProt:Q46865

Relationship Links: PDB:Structure:3HI2

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0017148 - negative regulation of translation Inferred from experiment [Yamaguchi09]
GO:0043488 - regulation of mRNA stability Inferred from experiment [Yamaguchi09]
GO:0044010 - single-species biofilm formation Inferred from experiment [Gonzalez06a]
GO:0045892 - negative regulation of transcription, DNA-templated Inferred from experiment [Gonzalez06a]
GO:0090502 - RNA phosphodiester bond hydrolysis, endonucleolytic Inferred from experiment [Yamaguchi09]
GO:0006351 - transcription, DNA-templated Inferred by computational analysis [UniProtGOA11]
GO:0006355 - regulation of transcription, DNA-templated Inferred by computational analysis [UniProtGOA11]
GO:0009372 - quorum sensing Inferred by computational analysis [UniProtGOA11]
GO:0090305 - nucleic acid phosphodiester bond hydrolysis Inferred by computational analysis [UniProtGOA11]
Molecular Function: GO:0004521 - endoribonuclease activity Inferred from experiment [Yamaguchi09]
GO:0005515 - protein binding Inferred from experiment [Yamaguchi09]
GO:0004518 - nuclease activity Inferred by computational analysis [UniProtGOA11]
GO:0004519 - endonuclease activity Inferred by computational analysis [UniProtGOA11]
GO:0016787 - hydrolase activity Inferred by computational analysis [UniProtGOA11]

MultiFun Terms: cell processes motility, chemotaxis, energytaxis (aerotaxis, redoxtaxis etc)
regulation type of regulation posttranscriptional translation attenuation and efficiency

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Enzymatic reaction of: mRNA interferase

EC Number: 3.1.-.-

an mRNA + H2O <=> a single-stranded RNA + a single-stranded RNA

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Subunit of: MqsA-MqsR antitoxin/toxin complex

Synonyms: MqsAR

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of MqsA-MqsR antitoxin/toxin complex = [MqsA]2[MqsR]4
         MqsA antitoxin of the MqsRA toxin-antitoxin system and DNA-binding transcriptional repressor = MqsA (extended summary available)
         mRNA interferase, toxin of the MqsR-MqsA toxin-antitoxin system = MqsR (extended summary available)

Summary:
Based on biophysical and crystallographic studies, it was shown that MqsR is not a transcription corepressor but instead functions to destabilize the MqsA-DNA complex. The MqsRA complex does not bind to DNA [Brown13]. This is the first toxin-antitoxin (TA) system identified where the toxin does not function as a transcriptional corepressor [Brown13].

Credits:
Created in EcoCyc 22-Sep-2009 by Keseler I , SRI International
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Symmetry: Inverted Repeat


Sequence Features

Feature Class Location Citations Comment
Mutagenesis-Variant 55
[Brown09a, UniProt11]
Alternate sequence: A; UniProt: No change in toxicity.
Mutagenesis-Variant 56
[Brown09a, UniProt11]
Alternate sequence: A; UniProt: Loss of toxicity.
Mutagenesis-Variant 58
[Brown09a, UniProt11]
Alternate sequence: A; UniProt: No change in toxicity.
Mutagenesis-Variant 68
[Brown09a, UniProt11]
Alternate sequence: A; UniProt: Loss of toxicity.
Mutagenesis-Variant 72
[Brown09a, UniProt11]
Alternate sequence: A; UniProt: No change in toxicity.
Mutagenesis-Variant 81
[Brown09a, UniProt11]
Alternate sequence: A; UniProt: Loss of toxicity.
Mutagenesis-Variant 96
[Brown09a, UniProt11]
Alternate sequence: A; UniProt: Loss of toxicity.

History:
Peter D. Karp on Thu Jan 16, 2003:
Predicted gene function revised as a result of E. coli genome reannotation by Serres et al. [Serres01 ].
Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.


References

Brown09a: 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. PMID: 20041169

Brown13: 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);1286-94. PMID: 23172222

ChristensenDals10: Christensen-Dalsgaard M, Jorgensen MG, Gerdes K (2010). "Three new RelE-homologous mRNA interferases of Escherichia coli differentially induced by environmental stresses." Mol Microbiol 75(2);333-48. PMID: 19943910

Gonzalez06a: Gonzalez Barrios AF, Zuo R, Hashimoto Y, Yang L, Bentley WE, Wood TK (2006). "Autoinducer 2 controls biofilm formation in Escherichia coli through a novel motility quorum-sensing regulator (MqsR, B3022)." J Bacteriol 188(1);305-16. PMID: 16352847

Hong12a: Hong SH, Wang X, O'Connor HF, Benedik MJ, Wood TK (2012). "Bacterial persistence increases as environmental fitness decreases." Microb Biotechnol 5(4);509-22. PMID: 22221537

Kasari10: Kasari V, Kurg K, Margus T, Tenson T, Kaldalu N (2010). "The Escherichia coli mqsR and ygiT genes encode a new toxin-antitoxin pair." J Bacteriol 192(11);2908-19. PMID: 20233923

Kim10b: 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. PMID: 20105222

Kim10e: Kim Y, Wood TK (2010). "Toxins Hha and CspD and small RNA regulator Hfq are involved in persister cell formation through MqsR in Escherichia coli." Biochem Biophys Res Commun 391(1);209-13. PMID: 19909729

Luidalepp11: Luidalepp H, Joers A, Kaldalu N, Tenson T (2011). "Age of inoculum strongly influences persister frequency and can mask effects of mutations implicated in altered persistence." J Bacteriol 193(14);3598-605. PMID: 21602347

Reed03: Reed JL, Vo TD, Schilling CH, Palsson BO (2003). "An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM/GPR)." Genome Biol 4(9);R54. PMID: 12952533

Ren04: Ren D, Bedzyk LA, Thomas SM, Ye RW, Wood TK (2004). "Gene expression in Escherichia coli biofilms." Appl Microbiol Biotechnol 64(4);515-24. PMID: 14727089

Serres01: Serres MH, Gopal S, Nahum LA, Liang P, Gaasterland T, Riley M (2001). "A functional update of the Escherichia coli K-12 genome." Genome Biol 2(9);RESEARCH0035. PMID: 11574054

Shah06: Shah D, Zhang Z, Khodursky A, Kaldalu N, Kurg K, Lewis K (2006). "Persisters: a distinct physiological state of E. coli." BMC Microbiol 6;53. PMID: 16768798

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Wang11e: Wang X, Wood TK (2011). "Toxin-antitoxin systems influence biofilm and persister cell formation and the general stress response." Appl Environ Microbiol 77(16);5577-83. PMID: 21685157

Yamaguchi09: 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. PMID: 19690171

Yamaguchi11: Yamaguchi Y, Park JH, Inouye M (2011). "Toxin-antitoxin systems in bacteria and archaea." Annu Rev Genet 45;61-79. PMID: 22060041

Zhang08a: Zhang XS, Garcia-Contreras R, Wood TK (2008). "Escherichia coli transcription factor YncC (McbR) regulates colanic acid and biofilm formation by repressing expression of periplasmic protein YbiM (McbA)." ISME J 2(6);615-31. PMID: 18309357


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Fri Dec 19, 2014, BIOCYC13B.