What question did this study set out to answer?

This research aims to compare the photooxidation rates of RNA and DNA under singlet oxygen influence, highlighting distinct mechanisms.

April 26, 2026Open Access

Photosensitized oxidation of polyA-polyU-based RNAs incorporating a guanosine with a 1O2 trajectory pattern distinctive from that for DNA

TKTakashi KanamoriTokyo Institute of Technology NYNanai YoshidaTokyo Institute of Technology SKShota KanekoTokyo Institute of Technology

Key Points

This research aims to compare the photooxidation rates of RNA and DNA under singlet oxygen influence, highlighting distinct mechanisms.
Investigated photooxidation of RNA duplexes with varying photosensitizer-guanine distances.
Examined the impact of oxidation inhibitors like NaN3 and ascorbic acid.
Analyzed 1O2 consumption during the photooxidation process using furfuryl alcohol.
RNA duplex photooxidation proceeded approximately four times faster than DNA duplex oxidation.
Mechanism identified where the structure of RNA channels singlet oxygen, enhancing oxidation efficiency.
Confirmed that the photosensitizer is shielded from quenching by bulk H2O during the reaction.

Abstract

Nucleic acid oxidations can occur ubiquitously in cells. One such oxidation is caused by singlet oxygen (1O2) produced in cells, often changing the original function of nucleic acids. Previously, we demonstrated that 1O2 generated by photoirradiation of photosensitizers linked on the DNA duplex radially diffused out of the cylindrical surface, which ended in a poor guanine photooxidation efficiency. In this study, we found that the photooxidation of the corresponding RNA duplex proceeded about four times faster than that of the DNA duplex. In addition, we studied the photooxidation with RNA duplexes having different photosensitizer-guanine distances and an externally added photosensitizer, the oxidation inhibition with NaN3 and ascorbic acid, and the 1O2 consumption with furfuryl alcohol during the photooxidation. All the studies conducted here correspond to a mechanism in which the hollow in the double strand of a photosensitizer-linked antisense oligonucleotide and RNA provides a channel for 1O2 and a shield for the photosensitizer, protecting from quenching by bulk H2O, leading to an efficient photooxidation of RNA. The results obtained in this study will add a valuable information on the trajectory of 1O2 in the oxidation of RNAs.

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