Author Identifier (ORCID)

Fangli Hu: https://orcid.org/0000-0002-5188-3187

Wei Wang: https://orcid.org/0000-0002-1430-1360

Abstract

The central dogma of molecular biology, traditionally focused on nucleic acids and proteins, has historically overlooked the crucial involvement of carbohydrates (sugars/glycans) in cellular processes. Carbohydrates combine with lipids, proteins, and RNA to form glycoconjugates—glycolipids, glycoproteins, and glycoRNAs—that mediate signaling, recognition, and dynamic cellular responses. A glycomics-centered perspective within the paracentral dogma extends the central dogma by incorporating additional biomacromolecular modifications, illustrating how glycans function as context-dependent molecular signals synthesized through non-template enzymatic processes that are partly genetically constrained yet structurally unpredictable. Recognized as the “third alphabet of life” after nucleic acids (the first) and amino acids (the second), the glycan encodes rich information that regulates cellular communication, immunity, and disease processes.Glycoconjugates with the recently discovered glycoRNAs demonstrate how glycan modifications integrate with nucleic acids, while O-GlcNAcylation in DNA synthesis and DNA damage response, exemplified by O-GlcNAc transferase and O-GlcNAcase, modulates genome stability and cellular homeostasis. Advances in glycomics, framed within the concept of paracentral dogma, provide deep insights into glycoconjugates and their sugar-encoded information, offering novel avenues for vaccination, targeted interventions and glycomedicine.

Document Type

Journal Article

Date of Publication

1-1-2025

Publication Title

Proteomics

Publisher

Wiley

School

Nutrition and Health Innovation Research Institute / School of Medical and Health Sciences

Funders

Australia-China International Collaborative Grant (NH&MRC-APP1112767-NSFC81561128020) / National Natural Science Foundation of China (81273170, 81370083, 81673247, 81573215)

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Comments

This is an Author's Accepted Manuscript of: Cao, W., Hu, F., & Li, Y. (2025). Orthodox vs. paradox: Supporting the central dogma with sugar code. Proteomics. Advance online publication. https://doi.org/10.1002/pmic.70080

This article may be used for non‐commercial purposes in accordance with Wiley Terms and Conditions for Use of Self‐Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.

Available for download on Wednesday, November 18, 2026

Share

 
COinS
 

Link to publisher version (DOI)

10.1002/pmic.70080