5‐Oxyacetic Acid Modification Destabilizes Double Helical Stem Structures and Favors Anionic Watson–Crick like cmo5U‐G Base Pairs

Watson–Crick like G‐U mismatches with tautomeric Genol or Uenol bases can evade fidelity checkpoints and thereby contribute to translational errors. The 5‐oxyacetic acid uridine (cmo5U) modification is a base modification at the wobble position on tRNAs and is presumed to expand the decoding capabil...

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Bibliographic Details
Published in:Chemistry : a European journal 2018-12, Vol.24 (71), p.18903-18906
Main Authors: Strebitzer, Elisabeth, Rangadurai, Atul, Plangger, Raphael, Kremser, Johannes, Juen, Michael Andreas, Tollinger, Martin, Al‐Hashimi, Hashim M., Kreutz, Christoph
Format: Article
Language:English
Subjects:
Base pairs
Chemistry
Communication
Communications
Decoding
Double-stranded
Magnetic resonance spectroscopy
Melting curve
NMR spectroscopy
relaxation dispersion
Ribonucleic acid
RNA
RNA modifications
Stable isotopes
tRNA
Uridine
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Summary:Watson–Crick like G‐U mismatches with tautomeric Genol or Uenol bases can evade fidelity checkpoints and thereby contribute to translational errors. The 5‐oxyacetic acid uridine (cmo5U) modification is a base modification at the wobble position on tRNAs and is presumed to expand the decoding capability of tRNA at this position by forming Watson–Crick like cmo5Uenol‐G mismatches. A detailed investigation on the influence of the cmo5U modification on structural and dynamic features of RNA was carried out by using solution NMR spectroscopy and UV melting curve analysis. The introduction of a stable isotope labeled variant of the cmo5U modifier allowed the application of relaxation dispersion NMR to probe the potentially formed Watson–Crick like cmo5Uenol‐G base pair. Surprisingly, we find that at neutral pH, the modification promotes transient formation of anionic Watson–Crick like cmo5U−‐G, and not enolic base pairs. Our results suggest that recoding is mediated by an anionic Watson–Crick like species, as well as bring an interesting aspect of naturally occurring RNA modifications into focus—the fine tuning of nucleobase properties leading to modulation of the RNA structural landscape by adoption of alternative base pairing patterns. Changing the acidity: A detailed NMR spectroscopic investigation revealed the influence of the 5‐oxyacetic acid uridine modification on the RNA folding landscape. The modifier enhances the acidity of the uridine N3 proton leading to the formation of transient anionic Watson–Crick like U‐G base pairs even at neutral pH (see scheme).
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.201805077