PpGpp

The ribosome-associated ppGpp synthetase (RelA) is required for antibiotic production under the conditions of nitrogen limitation in S. coelicolor A3 and for cephamycin C production in S. clavuligerus. Deletion of the relA in S. coelicolor A3 results in the loss of production of the antibiotics actinorhodin (Act) and undecylprodigiosin (Red) and... 

Gralla JD, Escherichia coli ribosomal RNA transcription Regulatory roles for ppGpp, NTPs, architectural proteins and a polymerase-binding protein. Mol Microbiol 55 973-977, 2005. 

Ghakraburtty R, White J, Takano E, Bibb MJ, Gloning, characterization and disruption of a (p)ppGpp synthetase gene relA) of Streptomyces coelicolor K5 X), Mol Microbiol 19 357-368, 1996. 

Ghakraburtty R, Bibb MJ, The ppGpp synthetase gene relA) of Streptomyces coelicolor A3(2) plays a conditional role in antibiotic production and morphological differentiation,/Ais cferzti/179 5854-5861, 1997. 

The complex that RNA polymerase forms at the promoter site just prior to initiation. Some bacterial promoters require high NTP concentrations to initiate efficient transcription, because this represents a status report on the stores of ATP, UTP, GTP, and CTP needed for RNA synthesis. Nature has evolved a kinetic control device high initiating ATP and GTP concentrations must be present to stabilize an otherwise short-lived polymerase-promoter complex. The reader may also recall that bacterial translation is also tightly controlled, and amino acid starvation leads to ppGpp synthesis, the so-called stringent-response agent that also potently inhibits RNA polymerase. Such kinetic control ensures that NTP and amino acid concentrations are adequate before transcription and translation occur. 

Another regulatory nucleotide, ppGpp (Fig. 8-42), is produced in bacteria in response to a slowdown in protein synthesis during amino acid starvation. This nucleotide inhibits the synthesis of the rRNA and tRNA molecules (see Fig. 28-24) needed for protein synthesis, preventing the unnecessary production of nucleic acids. 

Guanosine 5 -diphosphate, 3-diphosphate (ppGpp) Nutritional stress Chapter 29... 

This is similar to the reaction by which guanosine 5-diphosphate 3 -diphosphate (ppGpp) is formed from GDP and ATP (Eq. 29-11). 

GCGCC-C —5 "discriminator" sequence inhibition of gene expression by ppGpp... 

Guanosine tetraphosphate (ppGpp) concentration under normal conditions, after amino acid starvation, and after readdition of amino acids ( = wild-type cells A = relA cells and = spoT cells). 

As stated earlier, rRNA synthesis is usually maintained at a rate proportional to the gross rate of protein synthesis. In a normal wild-type cell, when protein synthesis is limited (e.g., by amino acid availability), M. Cashel and J. Gallant have shown that the ppGpp concentration rises rapidly from about 50 pM to 500 /uM (fig. 30.16). Concomitantly, rRNA synthesis ceases abruptly. This is part of the phenotype known as the stringent response First, amino acid deprivation or other factors that slow down protein synthesis provoke an increased rate of accumulation of ppGpp thisin turn leads to an inhibition of rRNA synthesis. 

Observations on different mutants indicate that the —j concentration of ppGpp is regulated by a careful bal-... 

Schematic diagram of ppGpp synthesis and the hypothesized mechanism for its action. ppGpp is synthesized on the ribosome when there is a peptidyl-tRNA on the P site of the ribosome and uncharged tRNA on the A site. The ppGpp probably inhibits rRNA synthesis by complexing with the RNA polymerase.

This alteration of the RNA polymerase by ppGpp affects the ability of RNA polymerase to interact with promoters in a differential way. For the promoters of the rRNA operons, the polymerase-promoter interaction is strongly inhibited by ppGpp. For some other promoters the effect of ppGpp is actually stimulating. As first observed in the cell-... 

The observations on ppGpp s role in rRNA synthesis show that this nucleotide is an important control factor regulating rRNA synthesis, but it does not eliminate the possibility that other factors also affect the level of rRNA. In vivo and in vitro evidence indicates that the inhibitory effect of ppGpp on transcription extends to most tRNA and riboso-mal protein genes. Ribosomal protein gene expression also appears to be regulated at the translational level. 

Kramer, G. F., Baker, J. C., and Ames, B. N. (1988). Near-UV stress in Salmonella typhimurium 4-Thiouridine in tRNA, ppGpp, and ApppGpp as components of an adaptive response. J. Bacteriol. 170, 2344—2351. 

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