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Chapter 26 : Links between tRNA Modification and Metabolism and Modified Nucleosides as Tumor Markers

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Abstract:

tRNA is a key component in translation. The various tRNA species decode at different speeds and fidelity that depend on the availability of the tRNA species, of the codon choice, and of the codon context. Some tRNA may act as a cofactor in enzymatic reactions. The first precursor to porphyrins in many bacteria and organelles is glutamate-1-semialdehyde (GSA), which is formed after the ligation of Glu to tRNA. In bacteria, an unexpected link between tRNA modification and intermediary metabolism is the requirement of chorismic acid or its derivative in a previously unknown metabolic pathway to synthesize uridine-5-oxyacetic acid (cmoU34) and its methyl ester (mcmoU34). Thus, whereas links between tRNA modification and metabolism are well documented in bacteria, such links also exist in eukaryotes. In a study of human immunodeficiency virus (HIV)-positive intravenous heroin addicts, researchers found that serum ψ was an independent predictor of progression to AIDS in Centers for Disease Control and Prevention (CDC) stage A2 HIV-infected patients. Interestingly, queuine in higher organisms may have such a role, since it influences the physiology of the cell in a tRNA independent way. In multicellular organisms, there is turnover of stable RNA, and modified nucleosides are found intact in rather large amounts in serum and in the urine. Therefore, urinary excretion of modified nucleosides reflects the turnover of RNA. Most of the RNA, which contains modified nucleosides in the multicellular eukaryotes, is stable and participates in translation (rRNA and tRNA) or in splicing (the various U RNAs).

Citation: Björk G, Rasmuson T. 1998. Links between tRNA Modification and Metabolism and Modified Nucleosides as Tumor Markers, p 471-491. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch26

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Amino Acid Addition
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Aromatic Amino Acids
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Urinary Tract Infections
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Severe Combined Immunodeficiency
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Figure 1

Hypomodification of tRNA alters central and intermediary metabolism in bacteria. Mutants () defective in the hydroxylation of msiA37 to msioA37 in are unable (denoted −) and the mutant defective in the synthesis of mG37 has a reduced ability [denoted (−)] to grow on the indicated CAC cycle intermediates. An mutant of , which lacks msiA37 in its tRNA, grows better than the wild type (denoted ++; wild type is assumed to be +) on succinate or proline as a carbon source. Moreover, the Gnd enzyme is derepressed about twofold (denoted ↗) in the same mutant. Mutation in the gene, which results in lack of mG37 in the tRNA, apparently derepresses the synthesis of thiamine (denoted ↗). See text for references.

Citation: Björk G, Rasmuson T. 1998. Links between tRNA Modification and Metabolism and Modified Nucleosides as Tumor Markers, p 471-491. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch26
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