Gene Symbol: infC
Description: translation initiation factor IF-3
Alias: ECK1716, JW5829, fit, srjA
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. Antoun A, Pavlov M, Lovmar M, Ehrenberg M. How initiation factors maximize the accuracy of tRNA selection in initiation of bacterial protein synthesis. Mol Cell. 2006;23:183-93 pubmed
    ..We suggest why IF1 is essential for E. coli, discuss the role of the G-C base pairs in the anticodon stem of some tRNAs, and clarify gene expression changes with varying IF3 concentration in the living cell. ..
  2. Gualerzi C, Pon C. Initiation of mRNA translation in prokaryotes. Biochemistry. 1990;29:5881-9 pubmed
  3. Singh N, Das G, Seshadri A, Sangeetha R, Varshney U. Evidence for a role of initiation factor 3 in recycling of ribosomal complexes stalled on mRNAs in Escherichia coli. Nucleic Acids Res. 2005;33:5591-601 pubmed
    ..coli EFG in vivo and in vitro. These lines of evidence clearly demonstrate the physiological importance of IF3 in the overall mechanism of ribosome recycling in E.coli. ..
  4. Haggerty T, Lovett S. Suppression of recJ mutations of Escherichia coli by mutations in translation initiation factor IF3. J Bacteriol. 1993;175:6118-25 pubmed
    ..Mutational analysis of this plasmid mapped srjA to the infC gene encoding translation initiation factor 3 (IF3)...
  5. Boelens R, Gualerzi C. Structure and function of bacterial initiation factors. Curr Protein Pept Sci. 2002;3:107-19 pubmed
    ..In this article we outline the translation initiation process in bacteria and review these recent developments giving a summary of the main features of the structure and function of the initiation factors. ..
  6. Tedin K, Moll I, Grill S, Resch A, Graschopf A, Gualerzi C, et al. Translation initiation factor 3 antagonizes authentic start codon selection on leaderless mRNAs. Mol Microbiol. 1999;31:67-77 pubmed
    ..are corroborated by the observed increased translational efficiency of a leaderless reporter construct in an infC mutant strain unable to discriminate against non-standard start codons...
  7. Karimi R, Pavlov M, Buckingham R, Ehrenberg M. Novel roles for classical factors at the interface between translation termination and initiation. Mol Cell. 1999;3:601-9 pubmed
    ..We show that this step requires initiation factor IF3, whose role was previously thought to be restricted to promoting specific 30S initiation complex formation from free 30S subunits. ..
  8. O Connor M, Gregory S, RajBhandary U, Dahlberg A. Altered discrimination of start codons and initiator tRNAs by mutant initiation factor 3. RNA. 2001;7:969-78 pubmed
  9. Petrelli D, LaTeana A, Garofalo C, Spurio R, Pon C, Gualerzi C. Translation initiation factor IF3: two domains, five functions, one mechanism?. EMBO J. 2001;20:4560-9 pubmed
    ..The localization of IF3C far away from the decoding site and anticodon stem-loop of P-site-bound tRNA indicates that the IF3 fidelity function does not entail its direct contact with these structures. ..

More Information


  1. Maar D, Liveris D, Sussman J, Ringquist S, Moll I, Heredia N, et al. A single mutation in the IF3 N-terminal domain perturbs the fidelity of translation initiation at three levels. J Mol Biol. 2008;383:937-44 pubmed publisher
    ..A model illustrating how IF3 modulates an inherent function of the 30S subunit is discussed. ..
  2. De Cock E, Springer M, Dardel F. The interdomain linker of Escherichia coli initiation factor IF3: a possible trigger of translation initiation specificity. Mol Microbiol. 1999;32:193-202 pubmed
    ..A model is presented in which the extended linker would act as a 'strap', triggering a conformational change in the 30S subunit, which would then ensure initiator tRNA selection. ..
  3. Hirokawa G, Nijman R, Raj V, Kaji H, Igarashi K, Kaji A. The role of ribosome recycling factor in dissociation of 70S ribosomes into subunits. RNA. 2005;11:1317-28 pubmed
    ..The three-factor-dependent stable dissociation of ribosomes into subunits completes the ribosome cycle and the resulting subunits are ready for the next round of translation. ..
  4. Dallas A, Noller H. Interaction of translation initiation factor 3 with the 30S ribosomal subunit. Mol Cell. 2001;8:855-64 pubmed
    ..The N domain neighbors proteins S7 and S11 and may interfere with E site tRNA binding. Our model suggests that IF3 influences initiator tRNA selection indirectly. ..
  5. Moll I, Resch A, Blasi U. Discrimination of 5'-terminal start codons by translation initiation factor 3 is mediated by ribosomal protein S1. FEBS Lett. 1998;436:213-7 pubmed
    ..This suggests that 5'-terminal start codons are recognised by IF3 as non-standard because of the lack of 16S rRNA-mRNA contacts. ..
  6. Fabbretti A, Pon C, Hennelly S, Hill W, Lodmell J, Gualerzi C. The real-time path of translation factor IF3 onto and off the ribosome. Mol Cell. 2007;25:285-96 pubmed
    ..Upon 30S-50S association, IF3 dissociates concomitantly with the establishment of the 30S-50S bridges, following the reverse path of its binding with the IF3N-A790 interaction being lost before the IF3C-G700 interaction. ..
  7. Laursen B, Sørensen H, Mortensen K, Sperling Petersen H. Initiation of protein synthesis in bacteria. Microbiol Mol Biol Rev. 2005;69:101-23 pubmed
    ..The future challenge is to obtain atomic-resolution structures of complete initiation complexes in order to understand the mechanism of translation initiation in molecular detail. ..
  8. Moreau M, De Cock E, Fortier P, Garcia C, Albaret C, Blanquet S, et al. Heteronuclear NMR studies of E. coli translation initiation factor IF3. Evidence that the inter-domain region is disordered in solution. J Mol Biol. 1997;266:15-22 pubmed
    ..Such a high degree of flexibility of the inter-domain linker might be required for IF3 domains to interact with distant regions of the ribosome. ..
  9. Peske F, Rodnina M, Wintermeyer W. Sequence of steps in ribosome recycling as defined by kinetic analysis. Mol Cell. 2005;18:403-12 pubmed
    ..IF3 is required for the subsequent ejection of tRNA and mRNA from the small subunit. The latter step is slower than subunit dissociation and constitutes the rate-limiting step of ribosome recycling. ..
  10. Sacerdot C, Chiaruttini C, Engst K, Graffe M, Milet M, Mathy N, et al. The role of the AUU initiation codon in the negative feedback regulation of the gene for translation initiation factor IF3 in Escherichia coli. Mol Microbiol. 1996;21:331-46 pubmed
    The expression of the infC gene encoding translation initiation factor IF3 is negatively autoregulated at the level of translation, i.e...
  11. Antoun A, Pavlov M, Lovmar M, Ehrenberg M. How initiation factors tune the rate of initiation of protein synthesis in bacteria. EMBO J. 2006;25:2539-50 pubmed
    ..The reasons why IF1 and IF3 are essential in E. coli are discussed in the light of the present observations. ..
  12. Allen G, Zavialov A, Gursky R, Ehrenberg M, Frank J. The cryo-EM structure of a translation initiation complex from Escherichia coli. Cell. 2005;121:703-12 pubmed
    ..Additionally, we present evidence for the localization of IF1, IF3, one C-terminal domain of L7/L12, and the N-terminal domain of IF2 in the initiation complex. ..
  13. van der Hofstad G, Buitenhek A, Bosch L, Voorma H. Initiation factor IF-3 and the binary complex between initiation factor IF-2 and formylmethionyl-tRNA are mutually exclusive on the 30-S ribosomal subunit. Eur J Biochem. 1978;89:213-20 pubmed
    ..This implies that under our experimental conditions MS2 RNA binding precedes fMet-tRNA binding if one accepts that the presence of IF-3 on the 30-S subunit is obligatory for messenger binding. ..
  14. Garcia C, Fortier P, Blanquet S, Lallemand J, Dardel F. Solution structure of the ribosome-binding domain of E. coli translation initiation factor IF3. Homology with the U1A protein of the eukaryotic spliceosome. J Mol Biol. 1995;254:247-59 pubmed
    ..This suggests a convergent evolution process for these two proteins that are associated with ribonucleoproteic complexes. ..
  15. Elseviers D, Gallagher P, Hoffman A, Weinberg B, Schwartz I. Molecular cloning and regulation of expression of the genes for initiation factor 3 and two aminoacyl-tRNA synthetases. J Bacteriol. 1982;152:357-62 pubmed
    ..The results suggest that the genes for initiation factor 3 and phenylalanyl- and threonyl-tRNA synthetase are regulated by different mechanisms. ..
  16. Sette M, Spurio R, van Tilborg P, Gualerzi C, Boelens R. Identification of the ribosome binding sites of translation initiation factor IF3 by multidimensional heteronuclear NMR spectroscopy. RNA. 1999;5:82-92 pubmed
  17. Muralikrishna P, Wickstrom E. Inducible high expression of the Escherichia coli infC gene subcloned behind a bacteriophage T7 promoter. Gene. 1989;80:369-74 pubmed
    The gene for Escherichia coli translational initiation factor 3 (infC) has been inserted into an overexpression plasmid under the control of the bacteriophage T7 promoter...
  18. Yoshida H, Ueta M, Maki Y, Sakai A, Wada A. Activities of Escherichia coli ribosomes in IF3 and RMF change to prepare 100S ribosome formation on entering the stationary growth phase. Genes Cells. 2009;14:271-80 pubmed publisher
    ..This suggests that ribosomes change into forms which are hard to bind with IF3 and easy to form 100S ribosomes by RMF and HPF concomitantly with transition from the log phase to the stationary phase. ..
  19. Risuleo G, Gualerzi C, Pon C. Specificity and properties of the destabilization, induced by initiation factor IF-3, of ternary complexes of the 30-S ribosomal subunit, aminoacyl-tRNA and polynucleotides. Eur J Biochem. 1976;67:603-13 pubmed
    ..Several antibiotics have been tested for their capacity to interfere with this reaction; only high concentrations of tetracycline blocked this IF-3 activity. ..
  20. Lestienne P, Dondon J, Plumbridge J, Howe J, Mayaux J, Springer M, et al. Expression of the gene for Escherichia coli initiation factor IE-3 in vivo and in vitro. Eur J Biochem. 1982;123:483-8 pubmed
    ..A strain haploid for infC, the gene for IF-3, was modified to carry one or two additional infC genes giving diploid and triploid strains...
  21. Ayyub S, Dobriyal D, Varshney U. Contributions of the N- and C-Terminal Domains of Initiation Factor 3 to Its Functions in the Fidelity of Initiation and Antiassociation of the Ribosomal Subunits. J Bacteriol. 2017;199: pubmed publisher
    ..By generating complete and partial IF3 (infC) knockouts in Escherichia coli and by complementation analyses using various deletion constructs, we ..
  22. Fortier P, Schmitter J, Garcia C, Dardel F. The N-terminal half of initiation factor IF3 is folded as a stable independent domain. Biochimie. 1994;76:376-83 pubmed
    ..The N-terminal domain is very stable and comparison of its 2-D NMR spectrum with that of intact IF3 revealed that it retains its three-dimensional fold. ..
  23. Garcia C, Fortier P, Blanquet S, Lallemand J, Dardel F. 1H and 15N resonance assignments and structure of the N-terminal domain of Escherichia coli initiation factor 3. Eur J Biochem. 1995;228:395-402 pubmed
  24. Dass S, Jayaraman R. Intragenic suppression of the temperature-sensitivity caused by a mutation in a gene controlling transcription (fit) in Escherichia coli. Mol Gen Genet. 1985;198:299-303 pubmed
    Starting from a transcription-defective strain harbouring a temperature-sensitive mutation in the fit gene, a rifampicin-resistant, temperature-insensitive derivative has been isolated...
  25. Robertson E, Nicholson A. Phosphorylation of Escherichia coli translation initiation factors by the bacteriophage T7 protein kinase. Biochemistry. 1992;31:4822-7 pubmed
    ..These results provide the first evidence for the functional involvement of protein phosphorylation in the control of bacterial translation. ..
  26. Lomakin I, Shirokikh N, Yusupov M, Hellen C, Pestova T. The fidelity of translation initiation: reciprocal activities of eIF1, IF3 and YciH. EMBO J. 2006;25:196-210 pubmed
  27. Seshadri A, Varshney U. Mechanism of recycling of post-termination ribosomal complexes in eubacteria: a new role of initiation factor 3. J Biosci. 2006;31:281-9 pubmed
    ..However, in model 3, both the genetic and biochemical evidence support a more active role for IF3 even at the step of dissociation of the post-TC by RRF and EFG into the 50S and 30S subunits. ..
  28. Ganoza M, Aoki H, Burkhardt N, Murphy B. The ribosome as affinity matrix': efficient purification scheme for translation factors. Biochimie. 1996;78:51-61 pubmed
    ..The procedure markedly simplifies the isolation, in homogeneous form, of all the non-ribosomal proteins required to reconstruct translation. ..
  29. Giuliodori A, Brandi A, Gualerzi C, Pon C. Preferential translation of cold-shock mRNAs during cold adaptation. RNA. 2004;10:265-76 pubmed
    ..Finally, in contrast to a previous claim, translation of cold-shock cspA mRNA in the cold was found to be as sensitive as that of a non-cold-shock mRNA to both chloramphenicol and kanamycin inhibition. ..
  30. Lesage P, Chiaruttini C, Graffe M, Dondon J, Milet M, Springer M. Messenger RNA secondary structure and translational coupling in the Escherichia coli operon encoding translation initiation factor IF3 and the ribosomal proteins, L35 and L20. J Mol Biol. 1992;228:366-86 pubmed
    The Escherichia coli infC-rpmI-rplT operon encodes translation initiation factor IF3 and the ribosomal proteins, L35 and L20, respectively...
  31. Qin D, Abdi N, Fredrick K. Characterization of 16S rRNA mutations that decrease the fidelity of translation initiation. RNA. 2007;13:2348-55 pubmed
    ..This may indirectly stabilize fMet-tRNA(fMet) in the preinitiation complex and/or promote premature docking of the 50S subunit, resulting in increased levels of spurious initiation. ..
  32. Yoo J, RajBhandary U. Requirements for translation re-initiation in Escherichia coli: roles of initiator tRNA and initiation factors IF2 and IF3. Mol Microbiol. 2008;67:1012-26 pubmed publisher
    ..Strikingly, overexpression of IF3 also blocked E. coli from acting as a host for propagation of M13 phage. ..
  33. Brauer D, Wittmann Liebold B. The primary structure of the initiation factor IF-3 from Escherichia coli. FEBS Lett. 1977;79:269-75 pubmed
  34. Butler J, Springer M, Grunberg Manago M. AUU-to-AUG mutation in the initiator codon of the translation initiation factor IF3 abolishes translational autocontrol of its own gene (infC) in vivo. Proc Natl Acad Sci U S A. 1987;84:4022-5 pubmed
    ..We previously showed that Escherichia coli translation initiation factor IF3 regulates the expression of its own gene infC at the translational level in vivo...
  35. Subramanian A, Davis B. Activity of initiation factor F3 in dissociating Escherichia coli ribosomes. Nature. 1970;228:1273-5 pubmed
  36. Liveris D, Klotsky R, Schwartz I. Growth rate regulation of translation initiation factor IF3 biosynthesis in Escherichia coli. J Bacteriol. 1991;173:3888-93 pubmed
    b>infC, the gene encoding translation initiation factor IF3 in Escherichia coli, can be transcribed from three promoters...
  37. Singh N, Ahmad R, Sangeetha R, Varshney U. Recycling of ribosomal complexes stalled at the step of elongation in Escherichia coli. J Mol Biol. 2008;380:451-64 pubmed publisher
    ..coli. We show that the RRF-mediated process also alleviates the ung-stopless construct-mediated toxicity to the host by releasing the ung mRNA from the ribosomes harboring long-chain peptidyl-tRNAs. ..
  38. Brombach M, Pon C. The unusual translational initiation codon AUU limits the expression of the infC (initiation factor IF3) gene of Escherichia coli. Mol Gen Genet. 1987;208:94-100 pubmed
    The expression of infC, the structural gene for translational initiation factor IF3, has been studied in different constructs under the control of the lambda PL and tac promoters...
  39. Pramanik A, Wertheimer S, Schwartz J, Schwartz I. Expression of Escherichia coli infC: identification of a promoter in an upstream thrS coding sequence. J Bacteriol. 1986;168:746-51 pubmed
    b>infC, the gene which codes for translation initiation factor 3, is situated in a cluster in the genome of Escherichia coli with genes for several other components of the translation apparatus...
  40. Saraiya A, Lamichhane T, Chow C, SantaLucia J, Cunningham P. Identification and role of functionally important motifs in the 970 loop of Escherichia coli 16S ribosomal RNA. J Mol Biol. 2008;376:645-57 pubmed publisher
  41. Spurio R, Paci M, Pawlik R, La Teana A, DiGiacco B, Pon C, et al. Site-directed mutagenesis and NMR spectroscopic approaches to the elucidation of the structure-function relationships in translation initiation factors IF1 and IF3. Biochimie. 1991;73:1001-6 pubmed
  42. Elvekrog M, Gonzalez R. Conformational selection of translation initiation factor 3 signals proper substrate selection. Nat Struct Mol Biol. 2013;20:628-33 pubmed publisher
    ..Our results strongly support a conformational selection model in which the conformation of IF3 that is selectively stabilized within a completely and correctly assembled 30S IC facilitates further progress along the initiation pathway...
  43. Ling C, Ermolenko D. Initiation factor 2 stabilizes the ribosome in a semirotated conformation. Proc Natl Acad Sci U S A. 2015;112:15874-9 pubmed publisher
    ..Our results suggest that positioning subunits in a semirotated orientation facilitates subunit association and support a model in which L1 stalk movement is coupled to intersubunit rotation and/or IF2 binding. ..
  44. Chiaruttini C, Milet M, Springer M. Translational coupling by modulation of feedback repression in the IF3 operon of Escherichia coli. Proc Natl Acad Sci U S A. 1997;94:9208-13 pubmed
    ..The result is a novel type of translational coupling, where unfolding of the pseudoknot by ribosomes translating IF3 does not increase expression of L35 directly, but alleviates its repression by L20. ..
  45. Meinnel T, Sacerdot C, Graffe M, Blanquet S, Springer M. Discrimination by Escherichia coli initiation factor IF3 against initiation on non-canonical codons relies on complementarity rules. J Mol Biol. 1999;290:825-37 pubmed
    ..This suggests that IF3 somehow recognises codon-anticodon complementarity, at least at the second and third position of the codon, rather than some specific bases in either the codon or the anticodon. ..
  46. Qin D, Fredrick K. Control of translation initiation involves a factor-induced rearrangement of helix 44 of 16S ribosomal RNA. Mol Microbiol. 2009;71:1239-49 pubmed publisher
    ..These data provide evidence that the interaction between the initiator tRNA and the 30S P site is tuned to balance efficiency and accuracy during initiation. ..
  47. De Bellis D, Liveris D, Goss D, Ringquist S, Schwartz I. Structure-function analysis of Escherichia coli translation initiation factor IF3: tyrosine 107 and lysine 110 are required for ribosome binding. Biochemistry. 1992;31:11984-90 pubmed
  48. Lesage P, Truong H, Graffe M, Dondon J, Springer M. Translated translational operator in Escherichia coli. Auto-regulation in the infC-rpmI-rplT operon. J Mol Biol. 1990;213:465-75 pubmed
    The genes coding for translation initiation factor IF3 (infC) and for the ribosomal proteins L35 (rpmI) and L20 (rplT) are transcribed in that order from a promoter in front of infC...
  49. Wertheimer S, Klotsky R, Schwartz I. Transcriptional patterns for the thrS-infC-rplT operon of Escherichia coli. Gene. 1988;63:309-20 pubmed
    The genes coding for threonyl-tRNA synthetase (thrS), translation initiation factor 3 (infC) and ribosomal protein L20 (rplT) are clustered in the Escherichia coli genome...
  50. Kuroda A, Nomura K, Takiguchi N, Kato J, Ohtake H. Inorganic polyphosphate stimulates lon-mediated proteolysis of nucleoid proteins in Escherichia coli. Cell Mol Biol (Noisy-le-grand). 2006;52:23-9 pubmed
    ..Furthermore, Lon degraded His-tagged HupA protein efficiently in the presence of polyP. We also showed that degradation of the translational initiation factor InfC depends on polyP.
  51. Wu T, Wood D, Stein P, Comer M. Transcription of a gene cluster coding for two aminoacyl-tRNA synthetases and an initiation factor in Escherichia coli. J Mol Biol. 1984;173:177-209 pubmed
    ..closely together with the genes for threonyl-tRNA synthetase (thrS) and translation initiation factor IF3 (infC); the gene order is thrS infC pheS pheT...
  52. Springer M, Plumbridge J, Trudel M, Graffe M, Grunberg Manago M. Transcription units around the gene for E. coli translation initiation factor IF3 (infC). Mol Gen Genet. 1982;186:247-52 pubmed
    ..coli DNA fragments from around the structural gene for translation initiation factor IF3 (infC)...
  53. Petrelli D, Garofalo C, Lammi M, Spurio R, Pon C, Gualerzi C, et al. Mapping the active sites of bacterial translation initiation factor IF3. J Mol Biol. 2003;331:541-56 pubmed
    ..Overall, the results define two active surfaces in IF3C, and indicate that the different functions of IF3 rely on different molecular mechanisms involving separate active sites. ..
  54. Sussman J, Simons E, Simons R. Escherichia coli translation initiation factor 3 discriminates the initiation codon in vivo. Mol Microbiol. 1996;21:347-60 pubmed
    ..We discuss these observations as they relate to IF3 autoregulation and the mechanism of IF3 function. ..
  55. Springer M, Graffe M, Butler J, Grunberg Manago M. Genetic definition of the translational operator of the threonine-tRNA ligase gene in Escherichia coli. Proc Natl Acad Sci U S A. 1986;83:4384-8 pubmed
    ..These findings suggest that the ligase regulates its translation by binding to its mRNA at a place that shares some homology with its natural substrate. ..
  56. Giuliodori A, Brandi A, Giangrossi M, Gualerzi C, Pon C. Cold-stress-induced de novo expression of infC and role of IF3 in cold-shock translational bias. RNA. 2007;13:1355-65 pubmed
    Expression of Escherichia coli infC, which encodes translation initiation factor IF3 and belongs to a transcriptional unit containing several promoters and terminators, is enhanced after cold shock, causing a transient increase of the IF3/..
  57. Subramanian A, Ron E, Davis B. A factor required for ribosome dissociation in Escherichia coli. Proc Natl Acad Sci U S A. 1968;61:761-7 pubmed
  58. Plumbridge J, Springer M, Graffe M, Goursot R, Grunberg Manago M. Physical localisation and cloning of the structural gene for E. coli initiation factor IF3 from a group of genes concerned with translation. Gene. 1980;11:33-42 pubmed
    ..One plasmid, containing a 3.3 kb PstI fragment inserted into pBR322, does not code for any of the synthetase genes but causes strains carrying it to overproduce IF3. ..
  59. Fayat G, Mayaux J, Sacerdot C, Fromant M, Springer M, Grunberg Manago M, et al. Escherichia coli phenylalanyl-tRNA synthetase operon region. Evidence for an attenuation mechanism. Identification of the gene for the ribosomal protein L20. J Mol Biol. 1983;171:239-61 pubmed
    ..Further evidence is provided for this model by the features of pheS, T regulation in vivo (see the accompanying paper). ..
  60. Mayaux J, Fayat G, Fromant M, Springer M, Grunberg Manago M, Blanquet S. Structural and transcriptional evidence for related thrS and infC expression. Proc Natl Acad Sci U S A. 1983;80:6152-6 pubmed
    ..3], has been determined. The structural part of the gene is found upstream of and on the same DNA coding strand as infC, the gene for translational initiation factor IF3...
  61. Olsson C, Graffe M, Springer M, Hershey J. Physiological effects of translation initiation factor IF3 and ribosomal protein L20 limitation in Escherichia coli. Mol Gen Genet. 1996;250:705-14 pubmed
    ..the physiological roles of translation initiation factor IF3 and ribosomal protein L20 in Escherichia coli, the infC, rpmI and rpIT genes encoding IF3, L35 and L20, respectively, were placed under the control of lac promotor/..
  62. Hua Y, Raleigh D. On the global architecture of initiation factor IF3: a comparative study of the linker regions from the Escherichia coli protein and the Bacillus stearothermophilus protein. J Mol Biol. 1998;278:871-8 pubmed
    ..In addition, studies with mutant peptides show that the first Asp residue in the linker sequence helps to stabilize the helix via an N- capping interaction. ..