Potential nucleotide sites for RNA glycosylation: Acp3U and beyond

Abstract

The emerging field of glycoRNAs, RNA molecules covalently modified with glycans, challenges the long-held belief that glycosylation is exclusive to proteins and lipids. The discovery of 3-(3-amino-3-carboxypropyl) uridine (acp3U) as a specific N-glycan attachment site has been a major breakthrough, establishing glycoRNA as a structurally defined and functionally relevant biopolymer. This new function of acp3U suggests its crucial regulatory node that correlates translation with other cellular processes, such as immune modulation and cell signaling. The presence of glycoRNAs on the cell surface and their interaction with immune receptors imply their involvement in cell-to-cell communication. Furthermore, studies have begun to associate altered glycoRNA patterns with conditions like cancer and inflammation, opening up possibilities for diagnostic and therapeutic applications. Despite the rapid progress in this field, several key challenges remain, including the inherent bias of current detection methods, the difficulty of isolating pure glycoRNA samples from complex cellular mixtures, and the largely unknown mechanisms of specific glycan linkages. Future research must focus on developing unbiased and sensitive analytical technologies to accurately map these modification patterns at a single-nucleotide resolution. This review summarizes the chemical and enzymatic mechanisms of RNA glycosylation sites, highlights its potential functional roles in cells, and outlines future research aimed at uncovering its full biological and therapeutic potential.

Document Type

Journal Article

Date of Publication

12-17-2025

Volume

36

Issue

12

PubMed ID

41342401

Publication Title

Bioconjugate Chemistry

Publisher

ACS

School

School of Medical and Health Sciences

Funders

Shantou University Medical College Scientific Research Initiation Grant / First Affiliated Hospital of SUMC / Priority Academic Program Development of the Jiangsu Higher Education Institutes / Jiangsu Science and Technology Plan (BX2022023) / Jiangsu Shuangchuang Boshi Fund (JSSCBS20210697) / Suzhou Health Youth Talent Project (GSWS2022087) / Suzhou Science and Technology Plan (SYW2024037)

Comments

Wang, X., Deng, J., Miao, X., Ge, W., Jiang, J., Wang, W., & Yang, S. (2025). Potential nucleotide sites for RNA glycosylation: ACP3U and beyond. Bioconjugate Chemistry, 36(12), 2537–2550. https://doi.org/10.1021/acs.bioconjchem.5c00474

Copyright

subscription content

First Page

2537

Last Page

2550

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Link to publisher version (DOI)

10.1021/acs.bioconjchem.5c00474