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Biophysical Properties and Thermal Stability of Oligonucleotides of RNA Containing 7,8-Dihydro-8-hydroxyadenosine

Identifieur interne : 001D30 ( Main/Exploration ); précédent : 001D29; suivant : 001D31

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 : PMC:4302245

Descripteurs français

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. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 167–174, 2015.


Url:
DOI: 10.1002/bip.22579
PubMed: 25363418
PubMed Central: 4302245


Affiliations:


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<p>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 T
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