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Abstract:

This study explores covalently closed circular RNAs (cccRNAs) that lack out-of-frame stop codons, a feature that may enable reiterative translation. While reiterative translation has been demonstrated for one satellite RNA, our analysis reveals that overlapping circular ORFs lacking hidden stop codons are more frequent than expected by chance, especially as ORF length increases. Using viroid-like circular RNA datasets, we identify mitovirus RNA-dependent RNA polymerase (RdRP) sequences that preserve this stop-free property. Statistical analysis indicates that amino acid and codon usage biases contribute to maintaining this feature. These findings suggest that reiterative translation, alongside reiterative transcription, may be a strategy employed by mitovirus-like cccRNAs.