The nucleotide sequence of a ghutamine tRNA from rat liver

Chan, Jane C.; Yang, Julia A.; Dünn, Michael J.; Agris, Paul F.; Wong, Ting-Kam Leonard

doi:10.1093/nar/10.12.3755

Cited by 5 publications

(3 citation statements)

References 8 publications

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“…In the budding yeast Saccharomyces cerevisiae , three tRNAs are modified by addition of 5-methoxycarbonylmethyl (mcm 5 ) and 2-thio (s 2 ) groups to uridine at the 5′ nucleotide of the tRNA anticodon (U34), resulting in an mcm 5 s 2 U nucleotide. The m cm 5 s 2 U m odification (MSUM) and many of the responsible modifying enzymes are conserved across eukaryotes, having been identified in fungi [4], [5], plants [6], worms [7] and mammals [8]. Despite widespread conservation, and extensive biochemical characterization, the physiological role of MSUM is unknown.…”

Section: Introductionmentioning

confidence: 99%

Loss of a Conserved tRNA Anticodon Modification Perturbs Cellular Signaling

2013

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Transfer RNA (tRNA) modifications enhance the efficiency, specificity and fidelity of translation in all organisms. The anticodon modification mcm5s2U34 is required for normal growth and stress resistance in yeast; mutants lacking this modification have numerous phenotypes. Mutations in the homologous human genes are linked to neurological disease. The yeast phenotypes can be ameliorated by overexpression of specific tRNAs, suggesting that the modifications are necessary for efficient translation of specific codons. We determined the in vivo ribosome distributions at single codon resolution in yeast strains lacking mcm5s2U. We found accumulations at AAA, CAA, and GAA codons, suggesting that translation is slow when these codons are in the ribosomal A site, but these changes appeared too small to affect protein output. Instead, we observed activation of the GCN4-mediated stress response by a non-canonical pathway. Thus, loss of mcm5s2U causes global effects on gene expression due to perturbation of cellular signaling.

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Section: Introductionmentioning

confidence: 99%

Loss of a Conserved tRNA Anticodon Modification Perturbs Cellular Signaling

2013

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“…However, this binary view was challenged by findings showing that tRNA isoacceptors can be incompletely modified at specific positions [80–82]. Recent NGS-based mapping data also indicated the substoichiometric occurrence of RNA modifications in cRNAs.…”

Section: Rna Modification Research Comes Of Age: Conceptual Challengesmentioning

confidence: 99%

“…The high stoichiometry of some tractable RNA modifications, especially in ncRNAs, gave rise to the notion that RNA modifications are either present or absent from an RNA species. However, this binary view was challenged by findings showing that tRNA isoacceptors can be incompletely modified at specific positions [ 80 – 82 ]. Recent NGS-based mapping data also indicated the substoichiometric occurrence of RNA modifications in cRNAs.…”

Section: Rna Modification Research Comes Of Age: Conceptual Challengementioning

confidence: 99%

Understanding RNA modifications: the promises and technological bottlenecks of the ‘epitranscriptome’

2017

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The discovery of mechanisms that alter genetic information via RNA editing or introducing covalent RNA modifications points towards a complexity in gene expression that challenges long-standing concepts. Understanding the biology of RNA modifications represents one of the next frontiers in molecular biology. To this date, over 130 different RNA modifications have been identified, and improved mass spectrometry approaches are still adding to this list. However, only recently has it been possible to map selected RNA modifications at single-nucleotide resolution, which has created a number of exciting hypotheses about the biological function of RNA modifications, culminating in the proposition of the ‘epitranscriptome’. Here, we review some of the technological advances in this rapidly developing field, identify the conceptual challenges and discuss approaches that are needed to rigorously test the biological function of specific RNA modifications.

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