## 3 tRNA Core Modifications and Their Impact on Translation and Stress Adaptation  
### tRNA Modification Levels Depend on Growth Conditions  
Although tRNA modifications may appear to be constitutively introduced as static decoration on every tRNA of the cell, the level and/or nature of certain modifications in a tRNA population may change in response to environmental factors such as growth phase, temperature, cellular stresses or nutrient availability. These variations consist of the appearance, disappearance or change in the nature of the modification at the individual tRNA molecule level. Collectively, these variations have an impact on the level of modifications in tRNA populations [3].  
During the exponential growth phase, most microorganisms double their content on an hourly basis. In _E. coli_, the tRNA pool does not increase homogeneously during exponential growth. Instead, rare tRNAs tend to decrease in concentration while the concentration of other tRNAs remains apparently constant [116; 117; 118]. In _S. cerevisiae_, a similar phenomenon exists where tRNA proportions vary significantly upon stress, which may be part of stress response mechanisms [119]. These changes in tRNA proportions are linked to changes in tRNA modification status. Some abundant tRNAs are hypomodified during the exponential phase and complete their maturation during the stationary phase [116; 120]. In _E. coli_, abundant tRNAs tend to be less fully thiolated than tRNAs with rare codons [116]. In _B. subtilis_, more complete modifications are found in tRNAs from stationary cells in comparison with tRNAs of exponentially growing cells [120].  
In addition to the growth phase, growth conditions such as stress exposure, have been shown to affect tRNA modification levels in microorganisms. A pioneering study used HPLC-coupled mass spectrometry to quantitatively analyze modifications in tRNAs. The study showed that exposure to toxic substances such as methylmethane sulfonate (MMS), hydrogen peroxide (H\({}_{2}\)O\({}_{2}\)), sodium arsenite (NaAsO\({}_{2}\)) and sodium hypochlorite (NaOCI) in _S. cerevisiae_ affects the level of several modifications, many of which being tRNA core modifications [121]. Upon treatment with H\({}_{2}\)O\({}_{2}\), levels of m\({}^{5}\)C and m\({}_{2}^{2}\)G were increased, whereas levels of m\({}^{5}\)U, m\({}^{2}\)G and m\({}^{1}\)A were slightly decreased [121]. Various toxicants induced similar yet distinct changes in tRNA modifications, indicating that dynamic changes in tRNA modifications in response to cellular stresses are widespread and stress specific [121; 122]. Although the roles of these changes are still mostly unknown, some changes occurring at the wobble position have been interpreted in terms of modification-tunable expression of codon-biased genes (reviewed in [38; 39; 40; 41]). The possible role of the changes affecting tRNA core modifications upon stress exposure remains much less well characterized in comparison.  
Several other studies have reported alterations in the levels of tRNA core modifications upon exposure to various stresses or growth conditions. This includes, for instance, the Gm18 modification that is increased in _E. coli_ upon mild antibiotic stress [123]. In _S. cerevisiae_, additional m\({}^{5}\)C modifications are specifically introduced on tRNA\({}^{\rm Hs}\) at positions 48 and 50 in response to conditions characterized by global cell growth arrest [124]. In _T. thermophilus_, changes in the growth temperature were shown to affect levels of tRNA core modifications (see text above and references [94; 106]). In _E. coli_, heat stress and/or heat shock were also found to either increase or decrease the levels of several tRNA core modifications, e.g., s\({}^{4}\)U8/9, Gm18, m\({}^{7}\)G46 and acp\({}^{3}\)U47 [125]. These examples show that it is important to bear in mind that tRNA core modifications also undergo changes in response to stressful conditions and that this phenomenon is not limited to the modifications found at the wobble position.