The expanding role of cap-adjacent modifications in animals

Bellows, Eleanor; Fray, Rupert G.; Knight, Helen M.; Archer, Nathan

doi:10.3389/frnar.2024.1485307

The expanding role of cap-adjacent modifications in animals

Bellows, Eleanor; Fray, Rupert G.; Knight, Helen M.; Archer, Nathan

Authors

Dr Eleanor Bellows Eleanor.Bellows@nottingham.ac.uk
Research Fellow

Professor RUPERT FRAY RUPERT.FRAY@NOTTINGHAM.AC.UK
PROFESSOR OF EPITRANSCRIPTOMICS

Dr HELEN KNIGHT HELEN.KNIGHT@NOTTINGHAM.AC.UK
ASSOCIATE PROFESSOR

Dr NATHAN ARCHER Nathan.Archer@nottingham.ac.uk
Associate Professor

Abstract

Eukaryotic mRNA cap structures directly influence mRNA stability, translation, and immune recognition. While the significance of the mRNA cap itself has been well-established, recent research has revealed the intricate modifications to the nucleotides immediately adjacent to the cap. These include 2′-O-methylation (Cap1, Cap2) and N6-methyladenosine (m6Am), which recent work suggests may be dynamically regulated, interdependent, and vital for gene-regulation. This perspective explores the expanding role of cap-adjacent modifications. Cap1 is found on metazoan mRNA, viruses which infect metazoans, and the COVID-19 mRNA vaccines. We combined basic local alignment and 2D-TLC to track cap-adjacent modifying proteins and the modifications themselves to profile their prevalence throughout eukaryotes. We confirm that Cap1 is broadly metazoan specific, but surprisingly also in a brown algae. Additionally, we find genomic presence of the eraser, FTO more predictive of the occurrence of m6Am than the m6Am-writer, PCIF1. We then outline future directions to understand and exploit these enigmatic modifications.

Citation

Bellows, E., Fray, R. G., Knight, H. M., & Archer, N. (2024). The expanding role of cap-adjacent modifications in animals. Frontiers in RNA Research, 2, Article 1485307. https://doi.org/10.3389/frnar.2024.1485307

Journal Article Type	Article
Acceptance Date	Sep 18, 2024
Online Publication Date	Oct 1, 2024
Publication Date	Oct 1, 2024
Deposit Date	Oct 8, 2024
Publicly Available Date	Oct 1, 2024
Journal	Frontiers in RNA Research
Electronic ISSN	2813-7116
Publisher	Frontiers Media
Peer Reviewed	Peer Reviewed
Volume	2
Article Number	1485307
DOI	https://doi.org/10.3389/frnar.2024.1485307
Keywords	mRNA cap, mRNA, epicapome, epitranscriptome, gene expression, translation
Public URL	https://nottingham-repository.worktribe.com/output/40552642
Publisher URL	https://www.frontiersin.org/journals/rna-research/articles/10.3389/frnar.2024.1485307/full