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Nucleoside modifications in the regulation of gene expression: focus on tRNA | Cellular and Molecular Life Sciences
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Both, DNA and RNA nucleoside modifications contribute to the complex multi-level regulation of gene expression. Modified bases in tRNAs modulate protein translation rates in a highly dynamic manner. Synonymous codons, which differ by the third nucleoside in the triplet but code for the same amino acid, may be utilized at different rates according to codon–anticodon affinity. Nucleoside modifications in the tRNA anticodon loop can favor the interaction with selected codons by stabilizing specific base pairs. Similarly, weakening of base pairing can discriminate against binding to near-cognate codons. mRNAs enriched in favored codons are translated in higher rates constituting a fine-tuning mechanism for protein synthesis. This so-called codon bias establishes a basic protein level, but sometimes it is necessary to further adjust the production rate of a particular protein to actual requirements, brought by, e.g., stages in circadian rhythms, cell cycle progression or exposure to stress. Such an adjustment is realized by the dynamic change of tRNA modifications resulting in the preferential translation of mRNAs coding for example for stress proteins to facilitate cell survival. Furthermore, tRNAs contribute in an entirely different way to another, less specific stress response consisting in modification-dependent tRNA cleavage that contributes to the general down-regulation of protein synthesis. In this review, we summarize control functions of nucleoside modifications in gene regulation with a focus on recent findings on protein synthesis control by tRNA base modifications.
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Keywords {🔍}
pubmed, article, google, scholar, cas, trna, central, modifications, rna, translation, modification, trnas, wobble, protein, mitochondrial, cell, stress, base, position, codons, biol, mrna, nucleoside, codon, anticodon, mol, modified, human, mrnas, acids, methylation, res, chem, function, synthesis, proteins, control, halves, cells, structure, yeast, suzuki, nucleic, binding, genet, regulation, specific, cleavage, found, gene,
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article download pdf false watson–crick pairings histone acetyltransferase sin3/elp3 mto1 mediates tissue-specificity identical donor/acceptor pattern widespread post-transcriptional modifications von kleist-retzow jc post-transcriptionally modified nucleosides post-transcriptional modification steps growth phase-dependent alteration trna-derived rna fragments codon–anticodon affinity regulate transcriptome-wide mapping rapid transfer-rna deactivation rna epigenetics-chemical messages spring-loaded base modification trna-derived fragments contribute trna 5-methylaminomethyl-2-thiouridylate methyltransferase post-transcriptional modifications located base modification-mediated strengthening stabilizing codon–anticodon interactions purine-ending codons nna promotes cap-independent translation trm9-catalyzed trna modifications electron withdrawing/donating properties telomeric gene silencing intra-molecular cross-regulation modification-dependent trna cleavage gene expression affects prevailing mcm5h2u-trna product mitochondrial-trna modifier mto1 intrinsic codon–anticodon strength rna structure-specific manner ragged-red fiber disease cognate aminoacyl-trna synthetases mt-trna biochemical functions full size image n6-methyladenosine-dependent regulation 5′-cap-independent translation depends commonly base-methylated purines stress-induced cleavage rna-binding protein ybx1 3′utr-mediated translational control mt-trnas bearing ser mitochondria-specific 5-substituted pyrimidines cdk5rap1-mediated 2-methylthio modification codon–anticodon binding affinity murphy fv 4th correct mt-trna folding prevent frame-shift mutations
Questions {❓}
- Belostotsky R, Frishberg Y, Entelis N (2012) Human mitochondrial tRNA quality control in health and disease: a channelling mechanism?
- Grewal SS (2015) Why should cancer biologists care about tRNAs?
- How does this work?
- Lightowlers RN, Taylor RW, Turnbull DM (2015) Mutations causing mitochondrial disease: what is new challenges remain?
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headline:Nucleoside modifications in the regulation of gene expression: focus on tRNA
description:Both, DNA and RNA nucleoside modifications contribute to the complex multi-level regulation of gene expression. Modified bases in tRNAs modulate protein translation rates in a highly dynamic manner. Synonymous codons, which differ by the third nucleoside in the triplet but code for the same amino acid, may be utilized at different rates according to codon–anticodon affinity. Nucleoside modifications in the tRNA anticodon loop can favor the interaction with selected codons by stabilizing specific base pairs. Similarly, weakening of base pairing can discriminate against binding to near-cognate codons. mRNAs enriched in favored codons are translated in higher rates constituting a fine-tuning mechanism for protein synthesis. This so-called codon bias establishes a basic protein level, but sometimes it is necessary to further adjust the production rate of a particular protein to actual requirements, brought by, e.g., stages in circadian rhythms, cell cycle progression or exposure to stress. Such an adjustment is realized by the dynamic change of tRNA modifications resulting in the preferential translation of mRNAs coding for example for stress proteins to facilitate cell survival. Furthermore, tRNAs contribute in an entirely different way to another, less specific stress response consisting in modification-dependent tRNA cleavage that contributes to the general down-regulation of protein synthesis. In this review, we summarize control functions of nucleoside modifications in gene regulation with a focus on recent findings on protein synthesis control by tRNA base modifications.
datePublished:2016-04-19T00:00:00Z
dateModified:2016-04-19T00:00:00Z
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Regulation of gene expression
Modified nucleosides
Stress signaling
tRNA
Translation rate
Cell Biology
Biomedicine
general
Life Sciences
Biochemistry
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headline:Nucleoside modifications in the regulation of gene expression: focus on tRNA
description:Both, DNA and RNA nucleoside modifications contribute to the complex multi-level regulation of gene expression. Modified bases in tRNAs modulate protein translation rates in a highly dynamic manner. Synonymous codons, which differ by the third nucleoside in the triplet but code for the same amino acid, may be utilized at different rates according to codon–anticodon affinity. Nucleoside modifications in the tRNA anticodon loop can favor the interaction with selected codons by stabilizing specific base pairs. Similarly, weakening of base pairing can discriminate against binding to near-cognate codons. mRNAs enriched in favored codons are translated in higher rates constituting a fine-tuning mechanism for protein synthesis. This so-called codon bias establishes a basic protein level, but sometimes it is necessary to further adjust the production rate of a particular protein to actual requirements, brought by, e.g., stages in circadian rhythms, cell cycle progression or exposure to stress. Such an adjustment is realized by the dynamic change of tRNA modifications resulting in the preferential translation of mRNAs coding for example for stress proteins to facilitate cell survival. Furthermore, tRNAs contribute in an entirely different way to another, less specific stress response consisting in modification-dependent tRNA cleavage that contributes to the general down-regulation of protein synthesis. In this review, we summarize control functions of nucleoside modifications in gene regulation with a focus on recent findings on protein synthesis control by tRNA base modifications.
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Regulation of gene expression
Modified nucleosides
Stress signaling
tRNA
Translation rate
Cell Biology
Biomedicine
general
Life Sciences
Biochemistry
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