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Review

If the 5’ cap fits (wear it) – Non-canonical RNA capping

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Pages 1-13 | Received 10 Apr 2024, Accepted 18 Jun 2024, Published online: 15 Jul 2024
 

ABSTRACT

RNA capping is a prominent RNA modification that influences RNA stability, metabolism, and function. While it was long limited to the study of the most abundant eukaryotic canonical m7G cap, the field recently went through a large paradigm shift with the discovery of non-canonical RNA capping in bacteria and ultimately all domains of life. The repertoire of non-canonical caps has expanded to encompass metabolite caps, including NAD, FAD, CoA, UDP-Glucose, and ADP-ribose, alongside alarmone dinucleoside polyphosphate caps, and methylated phosphate cap-like structures. This review offers an introduction into the field, presenting a summary of the current knowledge about non-canonical RNA caps. We highlight the often still enigmatic biological roles of the caps together with their processing enzymes, focusing on the most recent discoveries. Furthermore, we present the methods used for the detection and analysis of these non-canonical RNA caps and thus provide an introduction into this dynamic new field.

Acknowledgments

We are grateful to members of the Cahova Group (Pavel Vopalensky, Ondrej Nesuta, and Maria Bianca Mititelu) for their help and advice. Figures were Created with BioRender.com. We acknowledge funding from the European Research Council Executive Agency (ERCEA) under the European Union’s Horizon Europe Framework Programme for Research and Innovation (grant agreement No. 101041374 – StressRNaction) and the Operational Programme Johannes Amos Comenius (OP JAC) project RNA for Therapy, reg. No. CZ.02.01.01/00/22_008/0004575 co-financed by the EU.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Ministry of Education, Youth and Sports [OP JAC, RNA4Therapy, CZ.02.01.01/00/22_008/0004575]; HORIZON EUROPE European Research Council [No. 101041374 – StressRNaction].