APOBEC3A deaminase catalyzes site-specific editing of transfer RNAs

Hoffa-Sobiech, K.; Sikora, J.; Ruszkowski, M.; Starczak, M.; Gackowski, D.; Blaszczak, A.; Mierzwa, A.; Rakoczy, M.; Marcinkowska-Swojak, M.; Stolarek, I.; Jackowiak, P.; Figlerowicz, M.; Budzko, L.

doi:10.1101/2025.06.10.658825

bioRxiv · 10.1101/2025.06.10.658825

APOBEC3A deaminase catalyzes site-specific editing of transfer RNAs

Hoffa-Sobiech, K.·Sikora, J.·Ruszkowski, M.·Starczak, M.·Gackowski, D.·Blaszczak, A.·Mierzwa, A.·Rakoczy, M.·Marcinkowska-Swojak, M.·Stolarek, I.·Jackowiak, P.·Figlerowicz, M.·Budzko, L.

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Abstract

APOBEC3A is a cytidine deaminase that plays a crucial role in innate immunity; however, it can also drive oncogenesis when dysregulated. While its DNA editing activity is well-studied, the impact of APOBEC3A on RNA has only recently gained attention. Previous studies revealed that APOBEC3A deaminates mRNA stem-loop structures, however, its activity on other RNA classes remains unexplored. Given its likely evolutionary origin from tRNA adenosine deaminases and the prevalence of stem-loop structures in tRNA, we investigated APOBEC3As activity on tRNAs. We found that in vitro APOBEC3A efficiently deaminates a large spectrum of tRNA isoacceptors, primarily at anticodon positions. To assess whether the editing sites identified in vitro can be detected in tumor tissues, we analyzed data from The Cancer Genome Atlas. We identified six editing sites present in numerous patient samples. Our results point to a possible impact of APOBEC3A on tRNA decoding capacity, with potential relevance to mistranslation and cancer development.

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Hoffa-Sobiech, K., Sikora, J., Ruszkowski, M., Starczak, M., Gackowski, D., Blaszczak, A., Mierzwa, A., Rakoczy, M., Marcinkowska-Swojak, M., Stolarek, I., Jackowiak, P., Figlerowicz, M., Budzko, L.. 2025-06-10. APOBEC3A deaminase catalyzes site-specific editing of transfer RNAs. https://doi.org/10.1101/2025.06.10.658825

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