Escherichia coli K-12 substr. MG1655 RNA: MicF small regulatory RNA

Gene: micF Accession Numbers: EG30063 (EcoCyc), b4439, ECK2208

Synonyms: stc

Superclasses: a regulatory RNA

Regulation Summary Diagram: ?

Regulation summary diagram for micF

The MicF small RNA [Andersen87] negatively regulates translation of the OmpF porin [Andersen89] and the stability of OmpF mRNA [Andersen89, Deighan00]. MicF binds to OmpF mRNA [Andersen90] and represses production of OmpF in response to environmental and/or stress conditions, including conditions of high osmolarity [Aiba87, Andersen89], low or moderate osmolarity [Ramani94], heat [Andersen89], ethanol [Andersen89], salicylate [Rosner91, Ramani01, Chubiz11], paraquat [Chou93], and membrane perturbation [Inoue97]. MicF activity has been implicated in resistance to antibiotic drugs [Cohen88, Hooper92, Chou93, Ariza95, Tanaka97, Balague01]. MicF is involved in survival of nitric oxide released by macrophages in response to infection [Nunoshiba93].

Additional targets of MicF have been defined and include regulation of Lrp expression in rich medium. A double negative feedback loop of MicF and Lrp regulation has been proposed [Holmqvist12].

The micF gene was originally found to encode a non-translated 174 nt antisense RNA that regulates OmpF abundance [Mizuno84]. It was later found that the primary transcript is a smaller, 93 nt RNA species [Andersen87]. The secondary structure of the MicF RNA has been examined [Schmidt95, Delihas97]. MicF is cleaved by RNase E in vitro [Schmidt95a] and may be destabilized by StpA [Deighan00] and is stabilized by Hfq [Urban07a].

MicF was found in a ribonucleoprotein complex [Andersen90]; it was later determined that MicF binds Hfq [Zhang03f, Windbichler08] and that regulation of OmpF [Urban07a] and Lrp [Holmqvist12] expression by MicF depends on the presence of Hfq. Regulation of OmpF does not depend on RNase E [Urban07a].

Overexpression of micF from a high-copy-number plasmid causes reduced OmpF expression, compared to wild type, while expression of micF from a low-copy-number plasmid does not appear to affect OmpF expression [Matsuyama85, Aiba87]. Deletion of micF suppresses the OmpF-defective phenotype of a tolC mutant, probably by upregulating production of OmpF [Misra85, Misra87]. The defect in OmpC regulation exhibited by a micF mutant is suppressed by HrsA overproduction [Utsumi96].

Regulation of micF expression has been described [Cohen88, Andersen89, Coyer90, Rosner91, Takayanagi91, Hooper92, Chou93, Gidrol93, Nunoshiba93, Li94a, Ramani94, Fawcett94, Ferrario95, Ariza95, Jair95, Jair96a, Jair96, Suzuki96, Li96a, Dukan96, Inoue97, Painbeni97, Bernstein99, Oh00b, Kwon00, Bennik00, Deighan00, Manchado00, Balague01, Dangi01, Ramani01, Miche03, Chen04].

Stc: "suppressor of TolC"

MicF: "mRNA-interfering complementary RNA" [Mizuno84]

Reviews: [Inouye88, Cambau93, Delihas95, Pratt96, Delihas97a, Wassarman99, Delihas01, Storz04, Gottesman04, Altuvia04, Guillier06, Vogel06, Gottesman06, De10, Delihas12]

Citations: [Komatsu90, Chen02, Tkachenko06]

Map Position: [2,311,106 -> 2,311,198] (49.81 centisomes, 179°)
Length: 93 bp

Genetic Regulation Schematic: ?

Genetic regulation schematic for micF

Unification Links: ASAP:ABE-0047259 , CGSC:18157 , EchoBASE:EB4226 , EcoGene:EG30063 , EcoliWiki:b4439 , PortEco:micF , RegulonDB:EG30063

GO Terms:

Biological Process: GO:0006979 - response to oxidative stress Inferred from experiment [Chou93]
GO:0034605 - cellular response to heat Inferred from experiment [Andersen89]
GO:0040033 - negative regulation of translation, ncRNA-mediated Inferred from experiment [Andersen89]
GO:0042493 - response to drug Inferred from experiment [Hooper92]
GO:0071474 - cellular hyperosmotic response Inferred from experiment [Ramani94, Andersen89]
Molecular Function: GO:0000499 - base pairing with mRNA Inferred from experiment [Andersen90]
GO:0000900 - translation repressor activity, nucleic acid binding Inferred from experiment [Holmqvist12]
GO:0005515 - protein binding Inferred from experiment [Zhang03f]
GO:0048027 - mRNA 5'-UTR binding Inferred from experiment [Andersen90]

MultiFun Terms: cell processes adaptations
cell processes defense/survival
cell processes protection drug resistance/sensitivity
information transfer RNA related antisense RNA
regulation type of regulation posttranscriptional antisense RNA
regulation type of regulation posttranscriptional translation attenuation and efficiency

Regulated Transcription Units (4 total): ?


Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Units:

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram


Suzanne Paley on Thu Oct 21, 2004:
Position updated based on U00096.2 release of genome
Markus Krummenacker on Mon Oct 20, 1997:
The location of this gene on the E. Coli chromosome has not yet been determined.

Last-Curated ? 01-Mar-2012 by Keseler I , SRI International


Aiba87: Aiba H, Matsuyama S, Mizuno T, Mizushima S (1987). "Function of micF as an antisense RNA in osmoregulatory expression of the ompF gene in Escherichia coli." J Bacteriol 169(7);3007-12. PMID: 2439487

Altuvia04: Altuvia S (2004). "Regulatory small RNAs: the key to coordinating global regulatory circuits." J Bacteriol 186(20);6679-80. PMID: 15466017

Andersen87: Andersen J, Delihas N, Ikenaka K, Green PJ, Pines O, Ilercil O, Inouye M (1987). "The isolation and characterization of RNA coded by the micF gene in Escherichia coli." Nucleic Acids Res 1987;15(5);2089-101. PMID: 2436145

Andersen89: Andersen J, Forst SA, Zhao K, Inouye M, Delihas N (1989). "The function of micF RNA. micF RNA is a major factor in the thermal regulation of OmpF protein in Escherichia coli." J Biol Chem 264(30);17961-70. PMID: 2478539

Andersen90: Andersen J, Delihas N (1990). "micF RNA binds to the 5' end of ompF mRNA and to a protein from Escherichia coli." Biochemistry 29(39);9249-56. PMID: 1702997

Ariza95: Ariza RR, Li Z, Ringstad N, Demple B (1995). "Activation of multiple antibiotic resistance and binding of stress-inducible promoters by Escherichia coli Rob protein." J Bacteriol 1995;177(7);1655-61. PMID: 7896685

Balague01: Balague C, Vescovi EG (2001). "Activation of multiple antibiotic resistance in uropathogenic Escherichia coli strains by aryloxoalcanoic acid compounds." Antimicrob Agents Chemother 45(6);1815-22. PMID: 11353631

Bennik00: Bennik MH, Pomposiello PJ, Thorne DF, Demple B (2000). "Defining a rob regulon in Escherichia coli by using transposon mutagenesis." J Bacteriol 182(13);3794-801. PMID: 10850996

Bernstein99: Bernstein C, Bernstein H, Payne CM, Beard SE, Schneider J (1999). "Bile salt activation of stress response promoters in Escherichia coli." Curr Microbiol 39(2);68-72. PMID: 10398829

Cambau93: Cambau E, Gutmann L (1993). "Mechanisms of resistance to quinolones." Drugs 45 Suppl 3;15-23. PMID: 7689446

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Chen04: Chen S, Zhang A, Blyn LB, Storz G (2004). "MicC, a second small-RNA regulator of Omp protein expression in Escherichia coli." J Bacteriol 186(20);6689-97. PMID: 15466019

Chou93: Chou JH, Greenberg JT, Demple B (1993). "Posttranscriptional repression of Escherichia coli OmpF protein in response to redox stress: positive control of the micF antisense RNA by the soxRS locus." J Bacteriol 175(4);1026-31. PMID: 7679383

Chubiz11: Chubiz LM, Rao CV (2011). "Role of the mar-sox-rob Regulon in Regulating Outer Membrane Porin Expression." J Bacteriol 193(9);2252-60. PMID: 21398557

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Coyer90: Coyer J, Andersen J, Forst SA, Inouye M, Delihas N (1990). "micF RNA in ompB mutants of Escherichia coli: different pathways regulate micF RNA levels in response to osmolarity and temperature change." J Bacteriol 172(8);4143-50. PMID: 1695892

Dangi01: Dangi B, Pelupessey P, Martin RG, Rosner JL, Louis JM, Gronenborn AM (2001). "Structure and dynamics of MarA-DNA complexes: an NMR investigation." J Mol Biol 314(1);113-27. PMID: 11724537

De10: De la Cruz MA, Calva E (2010). "The complexities of porin genetic regulation." J Mol Microbiol Biotechnol 18(1);24-36. PMID: 20068355

Deighan00: Deighan P, Free A, Dorman CJ (2000). "A role for the Escherichia coli H-NS-like protein StpA in OmpF porin expression through modulation of micF RNA stability." Mol Microbiol 38(1);126-39. PMID: 11029695

Delihas01: Delihas N, Forst S (2001). "MicF: an antisense RNA gene involved in response of Escherichia coli to global stress factors." J Mol Biol 313(1);1-12. PMID: 11601842

Delihas12: Delihas N (2012). "Regulating the regulator: MicF RNA controls expression of the global regulator Lrp." Mol Microbiol 84(3);401-4. PMID: 22380658

Delihas95: Delihas N (1995). "Regulation of gene expression by trans-encoded antisense RNAs." Mol Microbiol 15(3);411-4. PMID: 7540245

Delihas97: Delihas N (1997). "Antisense micF RNA and 5'-UTR of the target ompF RNA: phylogenetic conservation of primary and secondary structures." Nucleic Acids Symp Ser (36);33-5. PMID: 9478198

Delihas97a: Delihas N, Rokita SE, Zheng P (1997). "Natural antisense RNA/target RNA interactions: possible models for antisense oligonucleotide drug design." Nat Biotechnol 15(8);751-3. PMID: 9255788

Dukan96: Dukan S, Dadon S, Smulski DR, Belkin S (1996). "Hypochlorous acid activates the heat shock and soxRS systems of Escherichia coli." Appl Environ Microbiol 62(11);4003-8. PMID: 8899987

Fawcett94: Fawcett WP, Wolf RE (1994). "Purification of a MalE-SoxS fusion protein and identification of the control sites of Escherichia coli superoxide-inducible genes." Mol Microbiol 1994;14(4);669-79. PMID: 7891555

Ferrario95: Ferrario M, Ernsting BR, Borst DW, Wiese DE, Blumenthal RM, Matthews RG (1995). "The leucine-responsive regulatory protein of Escherichia coli negatively regulates transcription of ompC and micF and positively regulates translation of ompF." J Bacteriol 1995;177(1);103-13. PMID: 8002608

Gidrol93: Gidrol X, Farr S (1993). "Interaction of a redox-sensitive DNA-binding factor with the 5'-flanking region of the micF gene in Escherichia coli." Mol Microbiol 10(4);877-84. PMID: 7934849

Gottesman04: Gottesman S (2004). "The Small RNA Regulators of Escherichia coli: Roles and Mechanisms*." Annu Rev Microbiol 58;303-28. PMID: 15487940

Gottesman06: Gottesman S, McCullen CA, Guillier M, Vanderpool CK, Majdalani N, Benhammou J, Thompson KM, FitzGerald PC, Sowa NA, FitzGerald DJ (2006). "Small RNA regulators and the bacterial response to stress." Cold Spring Harb Symp Quant Biol 71;1-11. PMID: 17381274

Guillier06: Guillier M, Gottesman S, Storz G (2006). "Modulating the outer membrane with small RNAs." Genes Dev 20(17);2338-48. PMID: 16951250

Holmqvist12: Holmqvist E, Unoson C, Reimegard J, Wagner EG (2012). "A mixed double negative feedback loop between the sRNA MicF and the global regulator Lrp." Mol Microbiol 84(3);414-27. PMID: 22324810

Hooper92: Hooper DC, Wolfson JS, Bozza MA, Ng EY (1992). "Genetics and regulation of outer membrane protein expression by quinolone resistance loci nfxB, nfxC, and cfxB." Antimicrob Agents Chemother 36(5);1151-4. PMID: 1510409

Inoue97: Inoue K, Matsuzaki H, Matsumoto K, Shibuya I (1997). "Unbalanced membrane phospholipid compositions affect transcriptional expression of certain regulatory genes in Escherichia coli." J Bacteriol 179(9);2872-8. PMID: 9139902

Inouye88: Inouye M, Delihas N (1988). "Small RNAs in the prokaryotes: a growing list of diverse roles." Cell 53(1);5-7. PMID: 2450678

Jair95: Jair KW, Martin RG, Rosner JL, Fujita N, Ishihama A, Wolf RE (1995). "Purification and regulatory properties of MarA protein, a transcriptional activator of Escherichia coli multiple antibiotic and superoxide resistance promoters." J Bacteriol 1995;177(24);7100-4. PMID: 8522515

Jair96: Jair KW, Yu X, Skarstad K, Thony B, Fujita N, Ishihama A, Wolf RE (1996). "Transcriptional activation of promoters of the superoxide and multiple antibiotic resistance regulons by Rob, a binding protein of the Escherichia coli origin of chromosomal replication." J Bacteriol 1996;178(9);2507-13. PMID: 8626315

Jair96a: Jair KW, Fawcett WP, Fujita N, Ishihama A, Wolf RE (1996). "Ambidextrous transcriptional activation by SoxS: requirement for the C-terminal domain of the RNA polymerase alpha subunit in a subset of Escherichia coli superoxide-inducible genes." Mol Microbiol 1996;19(2);307-17. PMID: 8825776

Komatsu90: Komatsu T, Ohta M, Kido N, Arakawa Y, Ito H, Mizuno T, Kato N (1990). "Molecular characterization of an Enterobacter cloacae gene (romA) which pleiotropically inhibits the expression of Escherichia coli outer membrane proteins." J Bacteriol 172(7);4082-9. PMID: 2193928

Kwon00: Kwon HJ, Bennik MH, Demple B, Ellenberger T (2000). "Crystal structure of the Escherichia coli Rob transcription factor in complex with DNA." Nat Struct Biol 7(5);424-30. PMID: 10802742

Li94a: Li Z, Demple B (1994). "SoxS, an activator of superoxide stress genes in Escherichia coli. Purification and interaction with DNA." J Biol Chem 1994;269(28);18371-7. PMID: 8034583

Li96a: Li Z, Demple B (1996). "Sequence specificity for DNA binding by Escherichia coli SoxS and Rob proteins." Mol Microbiol 20(5);937-45. PMID: 8809747

Manchado00: Manchado M, Michan C, Pueyo C (2000). "Hydrogen peroxide activates the SoxRS regulon in vivo." J Bacteriol 182(23);6842-4. PMID: 11073934

Matsuyama85: Matsuyama S, Mizushima S (1985). "Construction and characterization of a deletion mutant lacking micF, a proposed regulatory gene for OmpF synthesis in Escherichia coli." J Bacteriol 162(3);1196-202. PMID: 3888961

Miche03: Miche L, Belkin S, Rozen R, Balandreau J (2003). "Rice seedling whole exudates and extracted alkylresorcinols induce stress-response in Escherichia coli biosensors." Environ Microbiol 5(5);403-11. PMID: 12713466

Misra85: Misra R, Reeves P (1985). "Molecular characterisation of the Stc- mutation of Escherichia coli K-12." Gene 40(2-3);337-42. PMID: 3007299

Misra87: Misra R, Reeves PR (1987). "Role of micF in the tolC-mediated regulation of OmpF, a major outer membrane protein of Escherichia coli K-12." J Bacteriol 169(10);4722-30. PMID: 2443485

Mizuno84: Mizuno T, Chou MY, Inouye M (1984). "A unique mechanism regulating gene expression: translational inhibition by a complementary RNA transcript (micRNA)." Proc Natl Acad Sci U S A 81(7);1966-70. PMID: 6201848

Nunoshiba93: Nunoshiba T, deRojas-Walker T, Wishnok JS, Tannenbaum SR, Demple B (1993). "Activation by nitric oxide of an oxidative-stress response that defends Escherichia coli against activated macrophages." Proc Natl Acad Sci U S A 90(21);9993-7. PMID: 8234347

Oh00b: Oh JT, Cajal Y, Skowronska EM, Belkin S, Chen J, Van Dyk TK, Sasser M, Jain MK (2000). "Cationic peptide antimicrobials induce selective transcription of micF and osmY in Escherichia coli." Biochim Biophys Acta 1463(1);43-54. PMID: 10631293

Painbeni97: Painbeni E, Caroff M, Rouviere-Yaniv J (1997). "Alterations of the outer membrane composition in Escherichia coli lacking the histone-like protein HU." Proc Natl Acad Sci U S A 94(13);6712-7. PMID: 9192630

Pratt96: Pratt LA, Hsing W, Gibson KE, Silhavy TJ (1996). "From acids to osmZ: multiple factors influence synthesis of the OmpF and OmpC porins in Escherichia coli." Mol Microbiol 20(5);911-7. PMID: 8809744

Ramani01: Ramani N, Boakye K (2001). "Salicylate inhibits the translation and transcription of ompF in Escherichia coli." Can J Microbiol 47(11);1053-7. PMID: 11766055

Ramani94: Ramani N, Hedeshian M, Freundlich M (1994). "micF antisense RNA has a major role in osmoregulation of OmpF in Escherichia coli." J Bacteriol 176(16);5005-10. PMID: 7519595

Rosner91: Rosner JL, Chai TJ, Foulds J (1991). "Regulation of ompF porin expression by salicylate in Escherichia coli." J Bacteriol 173(18);5631-8. PMID: 1715858

Schmidt95: Schmidt M, Zheng P, Delihas N (1995). "Secondary structures of Escherichia coli antisense micF RNA, the 5'-end of the target ompF mRNA, and the RNA/RNA duplex." Biochemistry 34(11);3621-31. PMID: 7534474

Schmidt95a: Schmidt M, Delihas N (1995). "micF RNA is a substrate for RNase E." FEMS Microbiol Lett 133(3);209-13. PMID: 8522136

Storz04: Storz G, Opdyke JA, Zhang A (2004). "Controlling mRNA stability and translation with small, noncoding RNAs." Curr Opin Microbiol 7(2);140-4. PMID: 15063850

Suzuki96: Suzuki T, Ueguchi C, Mizuno T (1996). "H-NS regulates OmpF expression through micF antisense RNA in Escherichia coli." J Bacteriol 178(12);3650-3. PMID: 8655567

Takayanagi91: Takayanagi K, Maeda S, Mizuno T (1991). "Expression of micF involved in porin synthesis in Escherichia coli: two distinct cis-acting elements respectively regulate micF expression positively and negatively." FEMS Microbiol Lett 67(1);39-44. PMID: 1723390

Tanaka97: Tanaka T, Horii T, Shibayama K, Sato K, Ohsuka S, Arakawa Y, Yamaki K, Takagi K, Ohta M (1997). "RobA-induced multiple antibiotic resistance largely depends on the activation of the AcrAB efflux." Microbiol Immunol 41(9);697-702. PMID: 9343820

Tkachenko06: Tkachenko AG, Pozhidaeva ON, Shumkov MS (2006). "Role of polyamines in formation of multiple antibiotic resistance of Escherichia coli under stress conditions." Biochemistry (Mosc) 71(9);1042-9. PMID: 17009960

Urban07a: Urban JH, Vogel J (2007). "Translational control and target recognition by Escherichia coli small RNAs in vivo." Nucleic Acids Res 35(3);1018-37. PMID: 17264113

Utsumi96: Utsumi R, Horie T, Katoh A, Kaino Y, Tanabe H, Noda M (1996). "Isolation and characterization of the heat-responsive genes in Escherichia coli." Biosci Biotechnol Biochem 60(2);309-15. PMID: 9063979

Vogel06: Vogel J, Papenfort K (2006). "Small non-coding RNAs and the bacterial outer membrane." Curr Opin Microbiol 9(6);605-11. PMID: 17055775

Wassarman99: Wassarman KM, Zhang A, Storz G (1999). "Small RNAs in Escherichia coli." Trends Microbiol 7(1);37-45. PMID: 10068996

Windbichler08: Windbichler N, von Pelchrzim F, Mayer O, Csaszar E, Schroeder R (2008). "Isolation of small RNA-binding proteins from E. coli: evidence for frequent interaction of RNAs with RNA polymerase." RNA Biol 5(1);30-40. PMID: 18388495

Zhang03f: Zhang A, Wassarman KM, Rosenow C, Tjaden BC, Storz G, Gottesman S (2003). "Global analysis of small RNA and mRNA targets of Hfq." Mol Microbiol 50(4);1111-24. PMID: 14622403

Other References Related to Gene Regulation

Baez13a: Baez A, Shiloach J (2013). "Escherichia coli avoids high dissolved oxygen stress by activation of SoxRS and manganese-superoxide dismutase." Microb Cell Fact 12;23. PMID: 23497217

Chubiz12: Chubiz LM, Glekas GD, Rao CV (2012). "Transcriptional cross talk within the mar-sox-rob regulon in Escherichia coli is limited to the rob and marRAB operons." J Bacteriol 194(18);4867-75. PMID: 22753060

Ernsting92: Ernsting BR, Atkinson MR, Ninfa AJ, Matthews RG (1992). "Characterization of the regulon controlled by the leucine-responsive regulatory protein in Escherichia coli." J Bacteriol 174(4);1109-18. PMID: 1346534

Gillette00: Gillette WK, Martin RG, Rosner JL (2000). "Probing the Escherichia coli transcriptional activator MarA using alanine-scanning mutagenesis: residues important for DNA binding and activation." J Mol Biol 299(5);1245-55. PMID: 10873449

Huang90: Huang L, Tsui P, Freundlich M (1990). "Integration host factor is a negative effector of in vivo and in vitro expression of ompC in Escherichia coli." J Bacteriol 1990;172(9);5293-8. PMID: 2203749

Mattison02: Mattison K, Oropeza R, Byers N, Kenney LJ (2002). "A phosphorylation site mutant of OmpR reveals different binding conformations at ompF and ompC." J Mol Biol 315(4);497-511. PMID: 11812125

Qin01: Qin L, Yoshida T, Inouye M (2001). "The critical role of DNA in the equilibrium between OmpR and phosphorylated OmpR mediated by EnvZ in Escherichia coli." Proc Natl Acad Sci U S A 98(3);908-13. PMID: 11158569

Rodionov01: Rodionov DA, Gelfand MS, Mironov AA, Rakhmaninova AB (2001). "Comparative approach to analysis of regulation in complete genomes: multidrug resistance systems in gamma-proteobacteria." J Mol Microbiol Biotechnol 3(2);319-24. PMID: 11321589

Tsung89: Tsung K, Brissette RE, Inouye M (1989). "Identification of the DNA-binding domain of the OmpR protein required for transcriptional activation of the ompF and ompC genes of Escherichia coli by in vivo DNA footprinting." J Biol Chem 1989;264(17);10104-9. PMID: 2656704

Viveiros07: Viveiros M, Dupont M, Rodrigues L, Couto I, Davin-Regli A, Martins M, Pages JM, Amaral L (2007). "Antibiotic stress, genetic response and altered permeability of E. coli." PLoS ONE 2;e365. PMID: 17426813

Yoshida06: Yoshida T, Qin L, Egger LA, Inouye M (2006). "Transcription regulation of ompF and ompC by a single transcription factor, OmpR." J Biol Chem 281(25):17114-23. PMID: 16618701

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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