The relationship between oxidative damage to nucleic acids and the biogenesis of disease e.g., cancer and neurological disorders, gives relevance to the studies of oxidative damaged nucleotides on DNA and RNA. In this research we investigated changes imposed by oxidative lesion 7,8-dihydro-8-hydroxyadenosine (8-oxoA) on single and double strands of RNA and in short hairpins. Measurements carried out on RNA:RNA homoduplex and RNA:DNA heteroduplex structures showed depressed melting temperature (T<sub>m</sub>) values of ca. 12-15 . We found that increasing the number of lesions resulted in larger destabilization, as reflected in their T<sub>m</sub> value (ca. 10 increments per modification). The presence of the oxidative lesion in short RNA hairpins yielded different results that depended on its position: stem and/or loop. Incorporation of 8-oxoA at the stem lead to structure inhibition, destabilization, or formation of other structures, i.e., increased loop size (tetraloop hexaloop/octaloop). On the other hand, no effect was observed upon incorporation at the first base within the loop. Structural studies were carried out using Circular Dichroism, Mass Spectroscopy, and Gel Electrophoresis. Overall, this study shows that the effects of 8-oxoA on RNA structure are dependent on both the amount of damage and its position. While destabilization of the secondary structures may be beneficial, due to faster degradation of the strand, stabilization may result in survival of the oxidized species and altered functionality.

Structural studies of oligonucleotides of RNA containing 7,8-dihydro-8-hydroxyadenosine

249th National Meeting (2015)

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