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Biophysical properties and thermal stability of oligonucleotides of RNA containing 7,8-dihydro-8-hydroxyadenosine.

Identifieur interne : 001621 ( PubMed/Checkpoint ); précédent : 001620; suivant : 001622

Biophysical properties and thermal stability of oligonucleotides of RNA containing 7,8-dihydro-8-hydroxyadenosine.

Auteurs : Ana M. Chauca-Diaz ; Yu Jung Choi ; Marino J E. Resendiz

Source :

RBID : pubmed:25363418

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English descriptors

Abstract

Circular dichroism (CD) was used to assess the stabilization/destabilization imposed by oxidative lesion 7,8-dihydro-8-hydroxyadenosine (8-oxoA) on strands of RNA with different structural motifs. RNA:RNA homoduplex destabilization was observed in a position dependent manner using 10-mers as models that displayed differences between 12.7 and 15.1°C. We found that increasing the number of modifications resulted in depressed Tm values of about 12-15°C per lesion. The same effect was observed on RNA:DNA heteroduplex samples. We also tested the effects of this lesion in short hairpins containing the tetraloop UUCX (X = A, 8-oxoA). We found that the stem was hypersensitive to substitution of A by 8-oxoA and that it destabilized the structure by >23°C. Concomitant substitution at the stem and loop prevented formation of this secondary structure or lead to other less-stable hairpins. Incorporation of this lesion at the first base of the loop had no effect on either structure. Overall, we found that the effects of 8-oxoA on RNA structure are position dependent and that its stabilization may vary from sharp decreases to small increments, in some cases, leading to the formation of other more/less stable structures. These structural changes may have larger biological implications, particularly if the oxidatively modified RNA persists, thus leading to changes in RNA reactivity and function.

DOI: 10.1002/bip.22579
PubMed: 25363418


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<div type="abstract" xml:lang="en">Circular dichroism (CD) was used to assess the stabilization/destabilization imposed by oxidative lesion 7,8-dihydro-8-hydroxyadenosine (8-oxoA) on strands of RNA with different structural motifs. RNA:RNA homoduplex destabilization was observed in a position dependent manner using 10-mers as models that displayed differences between 12.7 and 15.1°C. We found that increasing the number of modifications resulted in depressed Tm values of about 12-15°C per lesion. The same effect was observed on RNA:DNA heteroduplex samples. We also tested the effects of this lesion in short hairpins containing the tetraloop UUCX (X = A, 8-oxoA). We found that the stem was hypersensitive to substitution of A by 8-oxoA and that it destabilized the structure by >23°C. Concomitant substitution at the stem and loop prevented formation of this secondary structure or lead to other less-stable hairpins. Incorporation of this lesion at the first base of the loop had no effect on either structure. Overall, we found that the effects of 8-oxoA on RNA structure are position dependent and that its stabilization may vary from sharp decreases to small increments, in some cases, leading to the formation of other more/less stable structures. These structural changes may have larger biological implications, particularly if the oxidatively modified RNA persists, thus leading to changes in RNA reactivity and function.</div>
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