Cover Feature: The Mysterious World of Non‐Canonical Caps – What We Know and Why We Need New Sequencing Techniques (ChemBioChem 3/2025)

Dive into the intriguing world of 5’ non-canonical RNA caps —unique modifications derived from metabolites and cofactors such as NAD, FAD, CoA, UDP-glucose, UDP-N-acetylglucosamine, and dinucleoside polyphosphates—that challenge the long-held belief that RNA is capped solely by N7-methylguanosine. This review 10.1002/cbic.202400604 by Flaminia Mancini and Hana Cahova highlights how cutting-edge techniques like LC-MS have uncovered these caps across all domains of life and evaluates existing sequencing methods, emphasizing the urgent need for innovative technologies to decipher their biological roles. Discover a rapidly evolving field that could reshape our understanding of RNA biology.