Pervasive short hairpin folding in non-encapsidated RNA viruses

Pervasive hairpin folding is strongly enriched in capsidless RNA viruses, with peHaPi(+) spanning nearly all ormycoviruses and a substantial fraction of narnaviruses across 817,234 GenBank sequences.

• Why it matters: Genome-wide RNA secondary structure may shape viral replication and host interactions, but its distribution and functional significance across virus groups has been unclear.
• What they did: The peHaPi metric was developed to quantify densely distributed stem-loop structures and applied genome-wide to 817,234 GenBank virus sequences, followed by comparative analyses of predicted stability, codon base-pairing, RdRp similarity, and virus-derived small RNAs.
• The result: Higher peHaPi scores are associated with more stable and constrained predicted RNA structures and altered codon base-pairing patterns, while small RNA data show no evidence of reduced siRNA response; peHaPi classification plus DNA-read subtraction identifies candidate highly divergent ormyco- and narnavirus contigs lacking detectable protein homology or recognizable RdRp signatures.