Differential codon usage: a safeguard against inappropriate expression of specialized genes?

Abstract

Recent work has suggested that rare codons are sometimes used for the regulation of specialized gene expression in bacteria. Moreover, the cellular levels of certain tRNAs may fluctuate with growth conditions. Evidence implicating such mechanisms in the control of photosynthesis in Rhodobacter, solventogenesis in Clostridium, sporulation in Streptomyces, and fimbrial phase variation in E. coli is summarized. It is suggested that such mechanisms will prove applicable to the control of numerous additional specialized functions, and that the empirical tools for testing this possibility are currently available.

Transcripts of the genes sacB, amyE, sacC and csn expressed in Bacillus subtilis under the control of the 5′ untranslated sacR region display different stabilities that can be modulated

“…The free energies of stabilization of the four terminators at the 3h end are all very similar, therefore excluding the hypothesis that the differential stability is caused by differences in hairpins, which are supposed to prevent exonucleases from degrading the coding sequence of the mRNA (Higgins et al, 1993). Finally, the reasons for the low stability of amyE and sacC transcripts could lie in the translation mechanism adapted to a particular growth phase (Saier, 1995), hence the features of the translation machinery of the exponential phase did not fit well with these transcripts. The double exponential decay of amyE mRNA in addition to the monophasic decay of the corresponding functional mRNA suggests that this mRNA exists in two different states in the cells : one state with a very short half-life, probably either unprotected or only poorly protected by ribosomes, and therefore highly sensitive to endonucleolytic attack, and the other ribosome-bound with a half-life within the same range as that of sacB and csn transcripts.…”

“…It has been noted that the expression of proteins can be controlled by codon usage according to the cellular levels of tRNA, which fluctuate with growth conditions and growth phase (Saier, 1995 ;Shields & Sharp, 1987 ;Karlin & Mrazek, 2000). However, the different gene fusions constructed were all expressed under the same growth conditions and during the same growth phase.…”

“…Pulse-chase experiments indicated that there were no specific bottlenecks in the secretion pathway of α-amylase and levanase to account for such differences, since the precursor form of each protein is efficiently processed (Leloup et al, 1997(Leloup et al, , 1999. Therefore, it was postulated that the mRNA steady-state level controlled by mRNA decay and\or translation mechanisms is adapted to a particular growth phase (Shields & Sharp, 1987 ;Saier, 1995).…”

tDNA locus polymorphism and ecto-chromosomal DNA insertion hot-spots are related to the phylogenetic group of Escherichia coli strains

“…Although several hypotheses have been made to explain the frequent association of ECDNA regions with tDNA loci (Cheetham & Katz, 1995;Hou, 1999;Reiter et al, 1989;Saier, 1995;Williams, 2002), it is still unclear why certain tDNAs are preferred ECDNA insertion sites. We can suggest several reasons why a tDNA is not an ECDNA insertion site, although none of them can fully explain our results.…”

Enhanced detection of tRNA isoacceptors by combinatorial oligonucleotide hybridization

“…Numerous observations suggest that transfer RNA, although primarily involved in amino acid activation, may also control gene expression at different levels (reviewed in Söll, 1993)+ For instance, bacterial development can be regulated by low-abundance tRNA isoacceptors that modulate the expression of genes containing matching rare codons (Saier, 1995)+ Proteolytic degradation of several polypeptides can be triggered by a tRNA-dependent posttranslational addition of amino acids to the amino terminal residues of the protein+ This represents another example of the physiological versatility of the tRNA (Varshavsky, 1996)+ Regulation of the expression of specific tRNAs has been reported in response to cellular differentiation and growing conditions (reviewed in Sprague, 1995)+ However, different pathological conditions have also been associated with changes in tRNA metabolism+ Although point mutations in mitochondrial tRNA genes have been linked to numerous neuromuscular diseases (Graeber & Muller, 1998), variations in tRNA modifications (Dirheimer et al+, 1995) or tRNA expression (Mukerjee & Goldfeder, 1976;White, 1997) are often found in conjunction with neoplastic cell proliferation+…”