Figure 4: Effects of edQTLs on edited dsRNA structures.

We looked at structural features that distinguish 27 edQTLs with effect size ⩾0.025 and 100 control variants in edited dsRNAs. (a) Cartoon dsRNA containing an editing site (red), base-paired nucleotides (blue) and non-base-paired nucleotides (green). (b) Fraction of edQTLs and control variants positioned at base-paired nucleotides. edQTLs are significantly more likely than control variants to be base-paired (Fisher’s exact test). (c) Cartoon depicting the comparison of dsRNA free energies between the two alleles for a hypothetical variant. (d) Difference in dsRNA free energies between the two alleles for edQTLs and control variants, calculated as the free energy of lower edited allele subtracted from the higher edited allele. The edQTLs have a significantly larger difference in free energy than the control variants, with the higher editing allele having lower (more stable) free energies (one-sided Mann–Whitney U-test). (e) Same cartoon dsRNA as in (a) showing base pair distances between stem nucleotides and the editing site. The editing site is centred at position zero and the portion of the editing site side of the stem transcriptionally downstream of the editing site as well as its paired portion of the ECS was classified as positive. (f) Base-pair distances from edQTLs and control variants to the editing site. The control variants tend to be significantly enriched at the 5′ end of the dsRNA (one-sided Mann–Whitney U-test).