# Control of Ribosome Synthesis During the Cell Division Cycles of _E. coli_ and _Synechococcus_
## 2 Control of r-protein synthesis in _E. coli_
### Control of rRNA synthesis in rapidly changing environments  
It is ironic that one of the first indications of the control of rRNA synthesis was the discovery of ppGpp as a possible effector molecule that represses rRNA synthesis in non-steady state growth conditions ([PERSON] and [PERSON], 1969). In cells subjected to amino acid starvation or cells that are entering or are in a stationary phase of growth, ppGpp concentration increased significantly above basal level while rRNA transcription is decreased. The role of ppGpp as an effector molecule that controls the rRNA synthesis is a complex one. In any case, the control of the rRNA synthesis has been found to be associated with the \(m\) promoter strength, the regulatory molecules, Fis, H-NS, and feedback regulators, ppGpp and NTP ([PERSON] et al., 1996; [PERSON] et al., 1997; [PERSON] et al., 2001; [PERSON] et al., 2002). The promoter strength of \(m\) operons is increased by the UP element ([PERSON] et al., 1993). Fis proteins enhance the binding of RNAP to promoters by direct interaction with the C-terminal domain of the alpha subunit of RNAP ([PERSON] et al., 1997; [PERSON] et al., 1998). The UP elements and trans-acting Fis protein ([PERSON] et al., 1990) are able to increase transcription at least 300-fold ([PERSON] et al., 1994). On the other hand, H-NS proteins inhibit the promoter activity at P1 ([PERSON] et al., 1998). However, how does ppGpp decrease \(m\) expression and how does iNTP increase \(m\) expression? Experimental results show that ppGpp binds to B, B' of RNAP and S\({}^{70}\)([PERSON] et al., 1998; [PERSON] et al., 2001; [PERSON] and [PERSON], 1995; [PERSON] et al., 2003). The effector-RNAP complex binds to the \(m\) promoters and decreases the half-life of the open complex at P1 promoter sites ([PERSON] et al., 2001) resulting in decreased transcription from \(m\) P1. In translation inhibited cells or when cells emerge from the stationary phase or when the growth media is enriched, ppGpp is decreased and iNTP is increased. iNTP binds to RNAP and the iNTP-RNAP complex increases the half-lives of the transcription complex thereby enhancing transcription rate of rRNA ([PERSON] et al., 2002). Is it possible that ppGpp and iNTP act also as feedback regulators linking promoter activities and the need for protein synthesis in conditions where the growth media are enriched ([PERSON] and [PERSON], 2003; [PERSON] et al., 2003)? Experiments were done to compare promoter activities in WT and _nus_B5, _rp_oA, and _A_fis strains (transcription-compromised mutants) as the media were nutritionally enriched ([PERSON] and [PERSON], 2003). The results showed that an increase in promoter activity correlated with observed increased concentrations of ATP (=iNTP) and decreased ppGpp concentration in mutant strains. It was concluded that ppGpp and iNTP serve as effectors in controlling rRNA synthesis and play significant roles in feedback regulation in linking \(m\) P1 activities to the demands for protein synthesis upon enriching the nutrition of the media. However, in cells transformed with multiple copies of \(m\) operons (_i.e._, an \(m\) dosage compensation experiment), results showed that decreased promoter activities were associated with a small decrease in ATP concentration; surprisingly ppGpp did not increase as expected. This result reinforced the notion that other signal molecules are involved in the ribosome feedback regulation model during balanced growth conditions. It should also be noted that ppGpp, Fis and H-NS proteins are not involved in the growth rate-dependent control of rRNA expression ([PERSON] et al., 1990; [PERSON] et al., 1998; [PERSON] et al., 2003). It is interesting to note that ppGpp has taken an additional function. In this case, ppGpp, a product of _spoT_ gene, is involved in adaptive responses to detrimental nutritional and physical conditions.