# 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
For example, during depletion of amino acid, carbon source, fatty acid, and exposure to weak emission of UV light, _spoT_-dependent ppGpp accumulation occurs and wasteful rRNA synthesis is inhibited [111, 110]. In addition, _spoT_-dependent ppGpp accumulation activates the synthesis of RpoS which in turn stimulates several stress-resistance genes (see [PERSON] et al., 1998). **Coordination of rRNA and r-protein syntheses in ribosome formation, an enigmatic problem**  
In the assembly of ribosome, r-proteins bind to rRNA as rRNA is being transcribed [110]. In this transcriptionally coupled ribosome assembly process, r-proteins added early onto the nascent rRNA were found to be present in greater quantities. The order of specific r-proteins added to rRNA in the _in vivo_ assembly process is similar to the order of r-protein added in _in vitro_ reconstitution of 30S ribosome [111]. The transcription of rRNA operons occurs in the order of 16S, 23S and 5S. The orderly transcription of rRNA genes, and the orderly binding of r-proteins to the nascent rRNA, suggests that transcriptions of rRNA and r-proteins are coordinately regulated by gene regulatory proteins. It is becoming clear that the crucial processes of ribosome assembly are the mechanisms that coordinate the regulation of rRNA and r-protein syntheses. Experiments performed several decades ago indicated that pools of rRNA and r-protein are not found in any appreciable size [111]. However, the synthesis of both rRNA and r-protein occurs immediately after the nutritional shift-up, while total protein production occurs several minutes later [111, 112, 113]. These observations suggest a logical progression of ribosome synthesis and total protein production. Results from subsequent investigations indicated that r-protein genes are regulated at the level of initiation of transcription during both steady state growth and nutritional shift-up [111, 112]. However, as indicated earlier, the transcriptional control of r-protein and rRNA syntheses by gene regulatory proteins has not yet been determined in _E. coli_. A rapid change in the nutritional environment brought about by the nutritional shift-up would result in an increased demand for ribosomes. Several responses are now known to occur following nutritional shift-up. Increase synthesis of both rRNA and r-protein synthesis occurs immediately. The increased rRNA synthesis is stimulated by an increase in INTP and decrease in ppGpp concentrations. However, the regulatory mechanisms that increase r-protein synthesis during the nutritional shift-up have not been determined. In any case, molecular effectors, ppGpp and INTP, act as feedback regulators in controlling the synthesis of rRNA. It should be noted, however, that feedback mechanisms by definition, operate after the r-protein, rRNA and ribosomes are produced. It appears, therefore, that feedback mechanisms by operational definition are not involved in coordinating the initiations of r-protein and rRNA syntheses  
There could be other models of ribosome synthesis that are not discussed above. Nevertheless, a major obstacle in constructing ribosome biosynthesis models is determining the coordinate regulation of r-protein and rRNA syntheses. The task of finding the regulatory molecules that coordinate the synthesis of both r-protein and rRNA in _E. coli_ prior to and during ribosome assembly is not an easy undertaking. **Cell division cycle and ribosome synthesis of a photoautotroph, _Synechococcus sp_ PCC 6301**  
The sequential order of macromolecular synthesis that occurs during the cell cycle in _Synechococcus_ permits orderly production of major cellular structures in the reproduction of daughter cells in light growth conditions [111]. The initiation of r-protein and rRNA transcriptions, DNA replication and cell growth do not occur in the dark [111]. Periodic macromolecular synthesis patterns occur at medium to fast growth rates, and the cell cycle displays distinct D\({}_{1}\), S, and D\({}_{2}\) phases [111].