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|Title:||Ion mobility-mass spectrometry reveals details of formation and structure for GAA·TCC DNA and RNA triplexes|
|Other Titles:||Ion Mobility-Mass Spectrometry Reveals Details of Formation and Structure for GAA(.)TCC DNA and RNA Triplexes|
|Citation:||Journal of the American Society for Mass Spectrometry, 2019; 30(1):103-112|
|Publisher:||American Chemical Society|
|Jiawei Li, Alexander Begbie, Belinda J. Boehm, Alexander Button, Charles Whidborne, Yannii Pouferis, David M. Huang, Tara L. Pukala|
|Abstract:||DNA and RNA triplexes are thought to play key roles in a range of cellular processes such as gene regulation and epigenetic remodeling and have been implicated in human disease such as Friedreich's ataxia. In this work, ion mobility-mass spectrometry (IM-MS) is used with supporting UV-visible spectroscopy to investigate DNA triplex assembly, considering stability and specificity, for GAA·TTC oligonucleotide sequences of relevance to Friedreich's ataxia. We demonstrate that, contrary to other examples, parallel triplex structures are favored for these sequences and that stability is enhanced by increasing oligonucleotide length and decreasing pH. We also provide evidence for the self-association of these triplexes, consistent with a proposed model of higher order DNA structures formed in Friedreich's ataxia. By comparing triplex assembly using DNA- and RNA-based triplex-forming oligonucleotides, we demonstrate more favorable formation of RNA triplexes, suggesting a role for their formation in vivo. Finally, we interrogate the binding properties of netropsin, a known polyamide triplex destabilizer, with RNA-DNA hybrid triplexes, where preference for duplex binding is evident. We show that IM-MS is able to report on relevant solution-phase populations of triplex DNA structures, thereby further highlighting the utility of this technology in structural biology. Our data therefore provides new insights into the possible DNA and RNA assemblies that may form as a result of GAA triplet repeats.|
|Keywords:||Ion mobility-mass spectrometry; DNA triplex; Friedreich's ataxia; gas-phase structural biology|
|Rights:||© American Society for Mass Spectrometry, 2018|
|Appears in Collections:||Chemistry and Physics publications|
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