Tailored Watson–Crick Pairing Partners for Xanthosine in RNA
Abstract
The deamination of guanosine nucleobases results in the formation of xanthosine (X)-containing RNA. This process formally resembles adenine deamination (A-to-I editing). The biological significance and basic chemical consequences of X-modified RNA are poorly understood. In this study, we examine xanthosine interactions with tailored pyrimidine nucleobases. We synthesized RNAs that provide either the 2,4-diaminopyrimidine C-nucleoside kappa (K) or 2-iminocytidine (2imC) as an "ideal" tridendate Watson-Crick pairing partner. For K-modified RNA, we used a phosphoramidite previously introduced for RNA solidphase synthesis. For 2imC-modified RNA, we developed access via synthetic 2-thiocytidine (2sC)-modified RNA, followed by osmium tetroxide (OsO 4 )-ammonium chloride (NH 4 Cl)-mediated transformation into 2imC-modified RNA. RNAs with K-X or 2imC-X base pairs indeed showed stable duplex formation with significantly higher melting temperatures than X-C or X-U containing RNAs and higher still than A-U or G-U containing RNA references. Furthermore, nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallographic structure analysis confirmed the tridendate Watson-Crick pair geometry of K-X within an RNA double helix. Our findings suggest that K-X and 2imC-X pairs could be used in RNA decoding processes, thereby expanding the RNA genetic alphabet. However, their potential for use in biochemical and cellular applications remains to be seen.
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BibTeX
@article{mair2026tailored,
title = {{Tailored Watson–Crick Pairing Partners for Xanthosine in RNA}},
author = {Stefan Mair and Anna Rázková and Karl Brillet and Catherina Gasser and Eric Ennifar and Ronald Micura},
journal = {Chemistry - A European Journal},
year = {2026},
month = sep,
doi = {10.1002/chem.202501860},
url = {https://hal.science/hal-05772521v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Tailored Watson–Crick Pairing Partners for Xanthosine in RNA
AU - Stefan Mair
AU - Anna Rázková
AU - Karl Brillet
AU - Catherina Gasser
AU - Eric Ennifar
AU - Ronald Micura
PY - 2026
DA - 2026/09/30
JO - Chemistry - A European Journal
DO - 10.1002/chem.202501860
UR - https://hal.science/hal-05772521v1
AB - The deamination of guanosine nucleobases results in the formation of xanthosine (X)-containing RNA. This process formally resembles adenine deamination (A-to-I editing). The biological significance and basic chemical consequences of X-modified RNA are poorly understood. In this study, we examine xanthosine interactions with tailored pyrimidine nucleobases. We synthesized RNAs that provide either the 2,4-diaminopyrimidine C-nucleoside kappa (K) or 2-iminocytidine (2imC) as an "ideal" tridendate Watson-Crick pairing partner. For K-modified RNA, we used a phosphoramidite previously introduced for RNA solidphase synthesis. For 2imC-modified RNA, we developed access via synthetic 2-thiocytidine (2sC)-modified RNA, followed by osmium tetroxide (OsO 4 )-ammonium chloride (NH 4 Cl)-mediated transformation into 2imC-modified RNA. RNAs with K-X or 2imC-X base pairs indeed showed stable duplex formation with significantly higher melting temperatures than X-C or X-U containing RNAs and higher still than A-U or G-U containing RNA references. Furthermore, nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallographic structure analysis confirmed the tridendate Watson-Crick pair geometry of K-X within an RNA double helix. Our findings suggest that K-X and 2imC-X pairs could be used in RNA decoding processes, thereby expanding the RNA genetic alphabet. However, their potential for use in biochemical and cellular applications remains to be seen.
SN - 0947-6539
SN - 1521-3765
ER -