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The expanding field of non-canonical RNA capping: New enzymes and mechanisms

Lookup NU author(s): Jana WiedermannovaORCiD, Dr Yulia Yuzenkova



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2021 The Authors.Recent years witnessed the discovery of ubiquitous and diverse 5′-end RNA cap-like modifications in prokaryotes as well as in eukaryotes. These non-canonical caps include metabolic cofactors, such as NAD + /NADH, FAD, cell wall precursors UDP-GlcNAc, alarmones, e.g. dinucleotides polyphosphates, ADP-ribose and potentially other nucleoside derivatives. They are installed at the 5′ position of RNA via template-dependent incorporation of nucleotide analogues as an initiation substrate by RNA polymerases. However, the discovery of NAD-capped processed RNAs in human cells suggests the existence of alternative post-transcriptional NC capping pathways. In this review, we compiled growing evidence for a number of these other mechanisms which produce various non-canonically capped RNAs and a growing repertoire of capping small molecules. Enzymes shown to be involved are ADP-ribose polymerases, glycohydrolases and tRNA synthetases, and may potentially include RNA 3′-phosphate cyclases, tRNA guanylyl transferases, RNA ligases and ribozymes. An emerging rich variety of capping molecules and enzymes suggests an unrecognized level of complexity of RNA metabolism.

Publication metadata

Author(s): Wiedermannova J, Julius C, Yuzenkova Y

Publication type: Review

Publication status: Published

Journal: Royal Society Open Science

Year: 2021

Volume: 8

Issue: 5

Online publication date: 19/05/2021

Acceptance date: 28/04/2021

ISSN (electronic): 2054-5703

Publisher: Royal Society Publishing


DOI: 10.1098/rsos.201979