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Cellular Regulation of Guanosine Tetraphosphate and Guanosine Pentaphosphate
Abstract
The Pleiotropic Cellular Response to Amino Acid Availability
Most cells possess the capacity to coordinately regulate a rich variety of physiological activities in response to nutritional abundance. Perhaps the most widely studied of these mechanisms is the bacterial response to limitation of any amino acid for protein synthesis. This response was first noted as a stringent dependence of RNA accumulation on amino acid availability (Sands and Roberts 1952; Pardee and Prestidge 1956; Gros and Gros 1958) and later termed the “stringent response” (Stent and Brenner 1961). A mutant strain in which this amino acid dependence was relaxed was encountered (Borek, Rockenbach and Ryan 1956). Stent and coworkers mapped the mutant allele at the “RNA Control” (RC) or relA locus (Alföldi, Stent and Clowes 1962). Many more mutants of this locus have since been isolated by Fiil and Friesen (1968), providing isogenic strain pairs in which the functions of the rel gene product may be experimentally isolated. Fiil (1969) has shown that the rel− allele is recessive to the wild type (rel+). Much less common are mutations in at least two other loci, relB (Lavallé 1965) and relC (Friesen, unpublished). Since little has been reported about these unusual classes of relaxed mutants, in this review we will deal exclusively with the relA locus.
Most cells possess the capacity to coordinately regulate a rich variety of physiological activities in response to nutritional abundance. Perhaps the most widely studied of these mechanisms is the bacterial response to limitation of any amino acid for protein synthesis. This response was first noted as a stringent dependence of RNA accumulation on amino acid availability (Sands and Roberts 1952; Pardee and Prestidge 1956; Gros and Gros 1958) and later termed the “stringent response” (Stent and Brenner 1961). A mutant strain in which this amino acid dependence was relaxed was encountered (Borek, Rockenbach and Ryan 1956). Stent and coworkers mapped the mutant allele at the “RNA Control” (RC) or relA locus (Alföldi, Stent and Clowes 1962). Many more mutants of this locus have since been isolated by Fiil and Friesen (1968), providing isogenic strain pairs in which the functions of the rel gene product may be experimentally isolated. Fiil (1969) has shown that the rel− allele is recessive to the wild type (rel+). Much less common are mutations in at least two other loci, relB (Lavallé 1965) and relC (Friesen, unpublished). Since little has been reported about these unusual classes of relaxed mutants, in this review we will deal exclusively with the relA locus.
Several immediate effects of withdrawing an amino acid can be anticipated, such as insufficient free amino acid for cognate tRNA aminoacylation and derepression of specific amino acid biosynthetic pathways (Neidhardt 1966). However, Table 1 summarizes a growing list...
DOI: http://dx.doi.org/10.1101/0.733-745