# Structural analysis of uridine modifications in solved RNA structures

## TL;DR

This paper analyzes the structural impact of six common uridine modifications in RNA using experimentally determined 3D structures.

## Contribution

The study provides a comprehensive structural analysis of six uridine modifications in RNA, revealing conformational preferences and interaction differences.

## Key findings

- Uridine modifications are predominantly found in ribosomal and transfer RNAs, often in hairpin structures.
- Most modifications show high structural similarity to unmodified uridines, with RMSD ≤ 1.0 Å.
- Modification-specific sugar pucker preferences and interaction differences were observed.

## Abstract

Naturally occurring uridine modifications in RNA play critical roles in modulating RNA stability, translation, and immune responses. While detection methods have advanced, a comprehensive structural analysis across experimentally determined RNA 3D structures remains limited. In this study, we systematically examined six uridine modifications—pseudouridine (PSU), 5-methyluridine (5MU), 3-methyluridine (UR3), O2′-methyluridine (OMU), 4-thiouridine (4SU), and 5,6-dihydrouridine (H2U)—using data from the Research Collaboratory for Structural Bioinformatics Protein Data Bank. After curation, we identified 2982 PSU, 736 5MU, 232 UR3, 429 OMU, 314 4SU, and 171 H2U residues across RNA-containing structures. These modifications were primarily found in ribosomal and transfer RNAs, often localized within hairpin secondary structures. Sugar pucker analysis revealed modification-specific preferences for C3′-endo and C2′-endo conformations. To assess structural impacts, we generated sequence-representative structures and compared modified versus unmodified forms using all-atom root-mean-square deviation analysis. Most modifications showed high similarity to their unmodified counterparts (RMSD \documentclass[12pt]{minimal}
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