Control of bacterial transcription, translation and replication by (p)ppGpp.

The small nucleotides pppGpp and ppGpp (or (p)ppGpp) are rapidly synthesized in response to nutritional stress. In Escherichia coli, the enzymes RelA and SpoT are triggered by different starvation signals to produce (p)ppGpp. In many Gram-positive bacteria this is carried out by RelA and two small homologs. (p)ppGpp, along with the transcription factor DksA, has profound effects on transcription initiation in E. coli. (p)ppGpp/DksA exert differential effects on promoters by playing upon their intrinsic kinetic parameters, and by facilitating the utilization of alternative sigma factors. (p)ppGpp also regulates replication and translation. These studies highlight (p)ppGpp as a key factor in bacterial physiology that responds rapidly to diverse stresses, by shutting down growth and priming cellular defensive and adaptive processes.

[1]  Melanie B. Berkmen,et al.  Still looking for the magic spot: the crystallographically defined binding site for ppGpp on RNA polymerase is unlikely to be responsible for rRNA transcription regulation. , 2008, Journal of molecular biology.

[2]  William J. Rice,et al.  Structure and Function of the Transcription Elongation Factor GreB Bound to Bacterial RNA Polymerase , 2003, Cell.

[3]  T. Nyström,et al.  Regulation of sigma factor competition by the alarmone ppGpp. , 2002, Genes & development.

[4]  Sarah E. Ades,et al.  ppGpp and DksA likely regulate the activity of the extracytoplasmic stress factor σE in Escherichia coli by both direct and indirect mechanisms , 2008, Molecular microbiology.

[5]  R. Wagner,et al.  Transcriptional Pausing of RNA Polymerase in the Presence of Guanosine Tetraphosphate Depends on the Promoter and Gene Sequence* , 1996, The Journal of Biological Chemistry.

[6]  J. E. Cabrera,et al.  Coupling the distribution of RNA polymerase to global gene regulation and the dynamic structure of the bacterial nucleoid in Escherichia coli. , 2006, Journal of structural biology.

[7]  D. Jin,et al.  The rpoB mutants destabilizing initiation complexes at stringently controlled promoters behave like "stringent" RNA polymerases in Escherichia coli. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[8]  S. Nandi,et al.  Mutation in the relA Gene of Vibrio cholerae Affects In Vitro and In Vivo Expression of Virulence Factors , 2003, Journal of bacteriology.

[9]  M. Bibb,et al.  The global role of ppGpp synthesis in morphological differentiation and antibiotic production in Streptomyces coelicolor A3(2) , 2007, Genome Biology.

[10]  M. Rodnina,et al.  The nucleotide-binding site of bacterial translation initiation factor 2 (IF2) as a metabolic sensor , 2006, Proceedings of the National Academy of Sciences.

[11]  E. Yagil,et al.  Guanosine 3',5'-bispyrophosphate (ppGpp) synthesis in cells of Escherichia coli starved for Pi , 1995, Journal of bacteriology.

[12]  E. Bouveret,et al.  Acyl carrier protein/SpoT interaction, the switch linking SpoT‐dependent stress response to fatty acid metabolism , 2006, Molecular microbiology.

[13]  S. Gottesman,et al.  Modulating RssB activity: IraP, a novel regulator of sigma(S) stability in Escherichia coli. , 2006, Genes & development.

[14]  A. Grossman,et al.  Stringent response in Escherichia coli induces expression of heat shock proteins. , 1985, Journal of molecular biology.

[15]  M. Nascimento,et al.  Three gene products govern (p)ppGpp production by Streptococcus mutans , 2007, Molecular microbiology.

[16]  S. Séror,et al.  The stringent response blocks DNA replication outside the ori region in Bacillus subtilis and at the origin in Escherichia coli. , 1991, Journal of molecular biology.

[17]  K. Tedin,et al.  The bacterial signal molecule, ppGpp, regulates Salmonella virulence gene expression , 2004, Molecular microbiology.

[18]  John W. Foster,et al.  DksA A Critical Component of the Transcription Initiation Machinery that Potentiates the Regulation of rRNA Promoters by ppGpp and the Initiating NTP , 2004, Cell.

[19]  C. Lima,et al.  Structural and biochemical analysis of the Obg GTP binding protein. , 2002, Structure.

[20]  Hyun-chul Lee,et al.  Immune response induced by Salmonella typhimurium defective in ppGpp synthesis. , 2006, Vaccine.

[21]  R. Hilgenfeld,et al.  Conformational antagonism between opposing active sites in a bifunctional RelA/SpoT homolog modulates (p)ppGpp metabolism during the stringent response [corrected]. , 2004, Cell.

[22]  T. Nyström,et al.  Identical, Independent, and Opposing Roles of ppGpp and DksA in Escherichia coli , 2007, Journal of bacteriology.

[23]  R. Rudner,et al.  Is There a Link between Mutation Rates and the Stringent Response in Bacillus subtilis? a , 1999, Annals of the New York Academy of Sciences.

[24]  M. Jiang,et al.  G-Protein Control of the Ribosome-Associated Stress Response Protein SpoT , 2007, Journal of Bacteriology.

[25]  F. Kawamura,et al.  Identification and functional analysis of novel (p)ppGpp synthetase genes in Bacillus subtilis , 2007, Molecular microbiology.

[26]  M. Swanson,et al.  A two‐component regulator induces the transmission phenotype of stationary‐phase Legionella pneumophila , 2002, Molecular microbiology.

[27]  H. Nakai,et al.  Translation factor IF2 at the interface of transposition and replication by the PriA‐PriC pathway , 2007, Molecular microbiology.

[28]  Melanie B. Berkmen,et al.  DksA potentiates direct activation of amino acid promoters by ppGpp , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Melanie B. Berkmen,et al.  rRNA Promoter Regulation by Nonoptimal Binding of σ Region 1.2: An Additional Recognition Element for RNA Polymerase , 2006, Cell.

[30]  Harvey Rubin,et al.  The role of RelMtb-mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[31]  A. Grossman,et al.  Nutritional Control of Elongation of DNA Replication by (p)ppGpp , 2007, Cell.

[32]  R. Gourse,et al.  An alternative strategy for bacterial ribosome synthesis: Bacillus subtilis rRNA transcription regulation , 2004, The EMBO journal.

[33]  S. Yokoyama,et al.  Structural Basis for Transcription Regulation by Alarmone ppGpp , 2004, Cell.

[34]  M. Chamberlin,et al.  A direct effect of guanosine tetraphosphate on pausing of Escherichia coli RNA polymerase during RNA chain elongation. , 1981, The Journal of biological chemistry.

[35]  M. Marahiel,et al.  Cloning and characterization of a relA/spoT homologue from Bacillus subtilis , 1997, Molecular microbiology.

[36]  P. Andrew,et al.  Listeria monocytogenes relA and hpt Mutants Are Impaired in Surface-Attached Growth and Virulence , 2002, Journal of bacteriology.

[37]  H. Malke,et al.  Life in protein‐rich environments: the relA‐independent response of Streptococcus pyogenes to amino acid starvation , 2000, Molecular microbiology.

[38]  R. Gourse,et al.  Mechanism of regulation of transcription initiation by ppGpp. I. Effects of ppGpp on transcription initiation in vivo and in vitro. , 2001, Journal of molecular biology.

[39]  S. Rosenberg,et al.  Mutation as a Stress Response and the Regulation of Evolvability , 2007, Critical reviews in biochemistry and molecular biology.

[40]  M. Hecker,et al.  Bacillus subtilis functional genomics: global characterization of the stringent response by proteome and transcriptome analysis , 2002, Journal of bacteriology.

[41]  Tetsuya Hayashi,et al.  ppGpp with DksA controls gene expression in the locus of enterocyte effacement (LEE) pathogenicity island of enterohaemorrhagic Escherichia coli through activation of two virulence regulatory genes , 2006, Molecular microbiology.

[42]  Daniel N. Wilson,et al.  Dissection of the mechanism for the stringent factor RelA. , 2002, Molecular cell.

[43]  B E Wright,et al.  The effect of the stringent response on mutation rates in Escherichia coli K‐12 , 1996, Molecular microbiology.

[44]  K. Ochi,et al.  Identification of the bacterial alarmone guanosine 5′-diphosphate 3′-diphosphate (ppGpp) in plants , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[45]  G. Schreiber,et al.  ppGpp-mediated regulation of DNA replication and cell division in Escherichia coli , 2004, Current Microbiology.

[46]  A. Costanzo,et al.  Growth Phase-Dependent Regulation of the Extracytoplasmic Stress Factor, σE, by Guanosine 3′,5′-Bispyrophosphate (ppGpp) , 2006, Journal of bacteriology.

[47]  Frederick R. Blattner,et al.  Transcription Profiling of the Stringent Response in Escherichia coli , 2007, Journal of bacteriology.

[48]  M. Cashel,et al.  The stringent response , 1996 .

[49]  R. Gourse,et al.  Mechanism of regulation of transcription initiation by ppGpp. II. Models for positive control based on properties of RNAP mutants and competition for RNAP. , 2001, Journal of molecular biology.

[50]  S. Gottesman,et al.  ppGpp regulation of RpoS degradation via anti-adaptor protein IraP , 2007, Proceedings of the National Academy of Sciences.

[51]  T. Nyström,et al.  The Role of the Alarmone (p)ppGpp in ςN Competition for Core RNA Polymerase* , 2003, The Journal of Biological Chemistry.

[52]  James J Foti,et al.  A bacterial G protein-mediated response to replication arrest. , 2005, Molecular cell.

[53]  J. Mekalanos,et al.  Regulation of the stringent response is the essential function of the conserved bacterial G protein CgtA in Vibrio cholerae , 2007, Proceedings of the National Academy of Sciences.

[54]  C. Albrecht,et al.  Iron limitation induces SpoT‐dependent accumulation of ppGpp in Escherichia coli , 2005, Molecular microbiology.

[55]  Shigeyuki Yokoyama,et al.  Regulation through the Secondary Channel—Structural Framework for ppGpp-DksA Synergism during Transcription , 2004, Cell.

[56]  R. G. Lloyd,et al.  RNA polymerase modulators and DNA repair activities resolve conflicts between DNA replication and transcription. , 2005, Molecular cell.