Towards a comprehensive understanding of RNA deamination: synthesis and properties of xanthosine-modified RNA

Mair, Stefan; Erharter, Kevin; Renard, Eva; Brillet, Karl; Brunner, Melanie; Lusser, Alexandra; Kreutz, Christoph; Ennifar, Eric; Micura, Ronald

doi:10.1093/nar/gkac477

Cited by 9 publications

(13 citation statements)

References 58 publications

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“…MALDI‐TOF MS analyses of the obtained RNA products showed the successful loading of Gly onto the parent RNA strands. In addition, we detected, after the enzymatic digestion of the RNA products, the partial conversion of guanosine to xanthosine by nitrosative deamination [67, 68] …”

Section: Resultsmentioning

confidence: 99%

Loading of Amino Acids onto RNA in a Putative RNA‐Peptide World

et al. 2023

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RNA is a molecule that can both store genetic information and perform catalytic reactions. This observed dualism places RNA into the limelight of concepts about the origin of life. The RNA world concept argues that life started from self-replicating RNA molecules, which evolved toward increasingly complex structures. Recently, we demonstrated that RNA, with the help of conserved non-canonical nucleosides, which are also putative relics of an early RNA world, had the ability to grow peptides covalently connected to RNA nucleobases, creating RNA-peptide chimeras. It is conceivable that such molecules, which combined the information-coding properties of RNA with the catalytic potential of amino acid side chains, were once the structures from which life emerged. Herein, we report prebiotic chemistry that enabled the loading of both nucleosides and RNAs with amino acids as the first step toward RNA-based peptide synthesis in a putative RNA-peptide world.

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Section: Resultsmentioning

confidence: 99%

Loading of Amino Acids onto RNA in a Putative RNA‐Peptide World

et al. 2023

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“…To achieve our goals, synthetic hurdles had to be taken first; those concerned access to the phosphoramidites of 1‐deazaguanosine (c 1 G), 3‐deazaguanosine (c 3 G), and xanthosine (X) needed for RNA solid‐phase synthesis. Since only for c 3 G containing RNA synthetic procedures were published, [35, 36] we have developed novel protocols for c 1 G and X modified RNA [37, 38] . A further requirement for our undertaking was the set‐up of a reliable and robust real‐time assay for direct monitoring of pistol ribozyme cleavage.…”

Section: Resultsmentioning

confidence: 99%

Scaling Catalytic Contributions of Small Self‐Cleaving Ribozymes

et al. 2022

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Nucleolytic ribozymes utilize general acid-base catalysis to perform phosphodiester cleavage. In most ribozyme classes, a conserved active site guanosine is positioned to act as general base, thereby activating the 2'-OH group to attack the scissile phosphate (γ-catalysis). Here, we present an atomic mutagenesis study for the pistol ribozyme class. Strikingly, "general base knockout" by replacement of the guanine N1 atom by carbon results in only 2.7-fold decreased rate. Therefore, the common view that γ-catalysis critically depends on the N1 moiety becomes challenged. For pistol ribozymes we found that γ-catalysis is subordinate in overall catalysis, made up by two other catalytic factors (α and δ). Our approach allows scaling of the different catalytic contributions (α, β, γ, δ) with unprecedented precision and paves the way for a thorough mechanistic understanding of nucleolytic ribozymes with active site guanines.

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“…Deamination is degradation through hydrolysis of the base, which can happen in acidic conditions. The sugar and base will remain attached, but the reaction will transform cytidine, adenosine and guanosine into uridine, inosine and xanthosine, respectively 66 . Therefore, this degradation pathway can theoretically change the coding sequence of the mRNA, which in turn would lead to amino acid mutations in the produced protein.…”

Section: Rna Degradation Pathways During Manufacturing and Storagementioning

confidence: 99%