OMA and OPA—Software-Supported Mass Spectra Analysis of Native and Modified Nucleic Acids

Nyakas, Adrien; Blum, Lorenz C.; Stucki, Stephanie; Reymond, Jean‐Louis; Schürch, Stefan

doi:10.1007/s13361-012-0529-1

Cited by 46 publications

(33 citation statements)

References 22 publications

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“…With experience, mapping modifications onto a single tRNA sequence is feasible by the manual approach described above. However, the introduction of new software tools [26, 27, 38, 39] has simplified and automated most of these sequence reconstruction and modification mapping steps. Pretreating the oligonucleotides to remove the terminal phosphate in a T1 digestion increases the fragmentation pattern in the tandem mass spectrum [40], which increases the number of recognition elements for software analysis.…”

Section: Resultsmentioning

confidence: 99%

Sequence mapping of transfer RNA chemical modifications by liquid chromatography tandem mass spectrometry

Ross

Cao

et al. 2016

Methods

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Mass spectrometry is a powerful analytical tool for identifying and characterizing structural modifications to the four canonical bases in RNA, information that is lost when using techniques such as PCR for RNA analysis. Here we described an updated method for sequence mapping of modified nucleosides in transfer RNA. This modification mapping approach utilizes knowledge of the modified nucleosides present in the sample along with the genome-derived tRNA sequence to readily locate modifications site-specifically in the tRNA sequence. The experimental approach involves isolation of the tRNA of interest followed by separate enzymatic digestion to nucleosides and oligonucleotides. Both samples are analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) and the data sets are then combined to yield the modification profile of the tRNA. Data analysis is facilitated by the use of unmodified sequence exclusion lists and new developments in software that can automate MS/MS spectral annotation. The method is illustrated using tRNA-Asn isolated from Thermus thermophilus.

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Section: Resultsmentioning

confidence: 99%

Sequence mapping of transfer RNA chemical modifications by liquid chromatography tandem mass spectrometry

Ross

Cao

et al. 2016

Methods

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“…[18] While fragmentation of duplexes is generally characterized by strand separation, increased formation of terminal and internal backbone fragments were found to complement strand separation of platinated duplexes (Fig. 3).…”

Section: Duplex-dnamentioning

confidence: 96%

Elucidation of Nucleic Acid–Drug Interactions by Tandem Mass Spectrometry

Hari¹,

Nyakas²,

Stucki³

et al. 2014

Chimia

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In continuation of the long tradition of mass spectrometric research at the University of Bern, our group focuses on the characterization of nucleic acids as therapeutic agents and as drug targets. This article provides a short overview of our recent work on platinated single-stranded and higher-order nucleic acids. Nearly three decades ago the development of soft ionization techniques opened a whole new chapter in the mass spectrometric analysis of not only nucleic acids themselves, but also their interactions with potential drug candidates. In contrast to modern next generation sequencing approaches, though, the goal of the tandem mass spectrometric investigation of nucleic acids is by no means the complete sequencing of genetic DNA, but rather the characterization of short therapeutic and regulatory oligonucleotides and the elucidation of nucleic acid-drug interactions. The influence of cisplatin binding on the gas-phase dissociation of nucleic acids was studied by the means of electrospray ionization tandem mass spectrometry. Experiments on native and modified DNA and RNA oligomers confirmed guanine base pairs as the preferred platination site and laid the basis for the formulation of a gas-phase fragmentation mechanism of platinated oligonucleotides. The study was extended to double-stranded DNA and DNA quadruplexes. While duplexes are believed to be the main target of cisplatin in vivo, the recently discovered DNA quadruplexes constitute another promising target for anti-tumor drugs owing to their regulatory functions in the cell cycle.

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“…78 This software can take inputted RNA sequences, calculate expected MS/MS sequence ladders and then compare the calculated ladders against experimental data to score the strength of the match. A different strategy was used by Sample et al , who created RoboOligo to handle de novo sequence analysis of modified oligoribonucleotides.…”

Section: Developments In Techniques and Instrumentationmentioning

confidence: 99%

Mass spectrometry of modified RNAs: recent developments

Wetzel

Limbach

2016

Analyst

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A common feature of ribonucleic acids (RNAs) is that they can undergo a variety of chemical modifications. As nearly all of these chemical modifications result in an increase in the mass of the canonical nucleoside, mass spectrometry has long been a powerful approach for identifying and characterizing modified RNAs. Over the past several years, significant advances have been made in method development and software for interpreting tandem mass spectra resulting in approaches that can yield qualitative and quantitative information on RNA modifications, often at the level of sequence specificity. We discuss these advances along with instrumentation developments that have increased our ability to extract such information from relatively complex biological samples. With the increasing interest in how these modifications impact the epitranscriptome, mass spectrometry will continue to play an important role in bioanalytical investigations revolving around RNA.

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OMA and OPA—Software-Supported Mass Spectra Analysis of Native and Modified Nucleic Acids

Cited by 46 publications

References 22 publications

Sequence mapping of transfer RNA chemical modifications by liquid chromatography tandem mass spectrometry

Sequence mapping of transfer RNA chemical modifications by liquid chromatography tandem mass spectrometry

Elucidation of Nucleic Acid–Drug Interactions by Tandem Mass Spectrometry

Mass spectrometry of modified RNAs: recent developments

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