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The knowledge of DNA deamination motifs preferred by individual APOBECs revealed APOBEC3A as a major source of hypermutation in cancer. However, the extent and relative contribution of specific APOBECs into RNA editing remains unclear as their preferred RNA-editing motifs have not been defined. Here, using a parallel DNA and RNA sequencing strategy, coupled with motif-centered statistical analyses, we sought to identify mRNA edits and diagnostic editing motifs in yeast and human cells overexpressing individual APOBEC enzymes. This approach revealed a prevailing global enrichment for the uCg trinucleotide motif with even greater preference to the motif\u2019s cytosines located in 3\u2019 base of a loop within a hairpin-loop secondary structure when APOBEC3A, but not any other tested APOBEC, was overexpressed. Further analysis revealed the APOBEC3A-like diagnostic motif enrichment in editing calls from human cancers and blood cells. The APOBEC3A-like editing motif also prevailed in the RNA genomes of SARS-CoV-2 pandemic isolates, as well as in infectious persistent rubella viruses, and in polioviruses emerging from live-attenuated vaccine strains. Together, our results indicate that APOBEC3A is the predominant global APOBEC RNA editor with a potential to impact cell physiology and viral evolution.<\/jats:p>","DOI":"10.64898\/2026.02.10.705151","type":"posted-content","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T16:21:11Z","timestamp":1770913271000},"source":"Crossref","is-referenced-by-count":1,"title":["APOBEC3A is the predominant global editor of cytosines in human mRNAs and in single-strand RNA viruses"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7828-3520","authenticated-orcid":false,"given":"Zachary W.","family":"Kockler","sequence":"first","affiliation":[{"name":"Genome Integrity & Structural Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC 27709, 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