Strand Structure Controls Photoinduced Self-Repair of RNA Uracil Dimers

When exposed to ultraviolet (UV) light, nucleic acids form photolesions, which hinder biomolecular recognition and biochemical functions. Recent evidence shows that, independently of enzymatic DNA repair, specific nucleobase sequences exhibit nonenzymatic self-repair via photoinduced electron transfer to the most common photolesions, cyclobutane pyrimidine dimers. In contrast, RNA self-repair remains poorly understood, with experimental results limited to the GAU=U sequence, which is characterized by self-repair yields that are approximately two times lower than that of its DNA equivalent, GAT=T. Here, we performed molecular dynamics simulations and excited-state quantum chemical calculations to explain the low efficiency of RNA self-repair. We show that strand structure and unfavorable orientation of nucleobases are the main factors, which destabilize reactive charge transfer states in RNA and reduce self-repair yields by promoting unreactive photorelaxation pathways. Consequently, owing to inherent structural differences, the photochemical properties of RNA cannot be inferred directly from UV-irradiation experiments performed for analogous DNA sequences.