AUTHOR=Bellows Eleanor , Fray Rupert G. , Knight Helen M. , Archer Nathan TITLE=The expanding role of cap-adjacent modifications in animals JOURNAL=Frontiers in RNA Research VOLUME=2 YEAR=2024 URL=https://www.frontiersin.org/journals/rna-research/articles/10.3389/frnar.2024.1485307 DOI=10.3389/frnar.2024.1485307 ISSN=2813-7116 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.