More Than Charged Base Loss — Revisiting the Fragmentation of Highly Charged Oligonucleotides

Nyakas, Adrien; Eberle, Rahel Patricia; Stucki, Stephanie; Schürch, Stefan

doi:10.1007/s13361-014-0873-4

Cited by 8 publications

(20 citation statements)

References 42 publications

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“…Moreover, the isotopic distributions between the theoretical and experimental isotopic clusters from cyanate-lost precursors were shown to be inconsistent. 39 Our data sets expanded on previous results and provided accurate isotopic cluster matches. We compared the occurrence frequency of these two types of partial base losses between different oligo sequences under several charge states.…”

Section: Cyanate Anion Losses From Rna Oligos With 3′-u Were Dominant...mentioning

confidence: 56%

“…The phenomenon of precursor charge-state-dependent base losses revealed that highly-charged RNA oligos increased the Coulomb repulsion between a charged nucleobase and the sugar, thus improving the chance of nucleobase release via glycosidic bond cleavage. 39 We then integrated seq-ion and nucleobase loss behavior data to determine how these trends changed quantitatively with the charge state. The data showed that the fractional abundance of seq-ions in the CID spectra decreased from 73% to 45%, whereas the neutral and charged nucleobase-loss precursor ions increased from 22% to 55%, when the charge state increased from -1 to -5 (Figure 6d).…”

Section: Nucleobase Losses From Precursors Were Markedly Increased At...mentioning

confidence: 99%

“…The released groups here were presumed to be the isocyanic acid (neutral) and the isomer cyanate anion; these have occasionally been reported in the literature in the context of RNA/DNA oligos' CID spectra. 39 However, the dissociation behaviors and the specificity of their occurrences had not been comprehensively reported in a large data set. Moreover, the isotopic distributions between the theoretical and experimental isotopic clusters from cyanate-lost precursors were shown to be inconsistent.…”

Section: Cyanate Anion Losses From Rna Oligos With 3′-u Were Dominant...mentioning

confidence: 99%

See 2 more Smart Citations

Charge-State-Dependent Collision-Induced Dissociation Behaviors of RNA Oligonucleotides via High-Resolution Mass Spectrometry

Sun

Zuo

Zhang

et al. 2023

Preprint

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Mass spectrometry (MS)-based analysis of RNA oligonucleotides (oligos) plays an increasingly important role in the development of RNA therapeutics and in epitranscriptomic studies. However, MS fragmentation behaviors of RNA oligos are understood insufficiently. In this study, we characterized the negative-ion-mode fragmentation behaviors of 26 synthetic RNA oligos of four to eight nucleotides (nt) in length by collision-induced dissociation (CID) using a high-resolution, accurate-mass instrument. We find that in the CID spectra acquired under the normalized collisional energy of 35%, ~70% of the total peak intensity belonged to sequencing ions (a-B, a, b, c, d, w, x, y, z), ~25% belonged to precursor ions with either complete or partial loss of a nucleobase in the form of a neutral or an anion, and the remainder were internal ions and anionic nucleobases. Of the sequencing ions, the most abundant species were y, c, w, a-B, and a ions. The charge state of the RNA precursor ions strongly affected their fragmentation behaviors. As the precursor charge increased from -1 to -5, the fractional intensity of sequencing ions in the CID spectra decreased, whereas the fractional intensity of precursor ions with neutral and/or charged losses of a nucleobase increased. Moreover, RNA oligos containing U, especially at the 3′ terminus, tended to produce precursors that lost HNCO and/or NCO-, which presumably corresponded to isocyanic acid and cyanate anion, respectively. These findings build a strong foundation for mechanistic understanding of RNA fragmentation by MS/MS, contributing to future automated identification of RNA oligos from their CID spectra in a more efficient way.

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Section: Cyanate Anion Losses From Rna Oligos With 3′-u Were Dominant...mentioning

confidence: 56%

Section: Nucleobase Losses From Precursors Were Markedly Increased At...mentioning

confidence: 99%

Section: Cyanate Anion Losses From Rna Oligos With 3′-u Were Dominant...mentioning

confidence: 99%

See 1 more Smart Citation

Charge-State-Dependent Collision-Induced Dissociation Behaviors of RNA Oligonucleotides via High-Resolution Mass Spectrometry

Sun

Zuo

Zhang

et al. 2023

Preprint

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“…The analysis of modified RNAs by tandem mass spectrometry has become routine thanks to numerous fundamental studies by several research groups. [62][63][64] Sequence-specific information can be generated by applying energy to intact RNA oligomers in the gas phase, leading to predictable backbone fragmentation, which can locate modifications. More specifically, when activated using collision induced dissociation (CID), oligoribonucleotides typically fragment along the phosphodiester backbone to generate two separate mass ladders.…”

Section: Tandem Mass Spectrometrymentioning

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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“…Although CID of oligonucleotides predominately generates a-B and w type fragment ions (nomenclature of McLuckey et al [3]), generation of unidentifiable product ions and alternative fragmentation pathways (in CID and other fragmentation techniques) have also been reported [12][13][14][15]. For example, Juhasz et al reported generation of six unusual/unidentifiable high intensity product ion peaks from the DNA oligonucleotide, CAC ACG CCA GT [12]; these authors purported that the presence of unidentifiable fragment ions may make MS based de novo sequencing of some oligonucleotides impractical [12].…”

Section: Introductionmentioning

confidence: 99%

DNA Oligonucleotide Fragment Ion Rearrangements Upon Collision-Induced Dissociation

Harper

Neumann

Solouki

2015

J. Am. Soc. Mass Spectrom.

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Abstract. Collision-induced dissociation (CID) of m/z-isolated w type fragment ions and an intact 5′ phosphorylated DNA oligonucleotide generated rearranged product ions. Of the 21 studied w ions of various nucleotide sequences, fragment ion sizes, and charge states, 18 (~86%) generated rearranged product ions upon CID in a Synapt G2-S HDMS (Waters Corporation, Manchester, England, UK) ion mobility-mass spectrometer. Mass spectrometry (MS), ion mobility spectrometry (IMS), and theoretical modeling data suggest that purine bases can attack the free 5′ phosphate group in w type ions and 5′ phosphorylated DNA to generate sequence permuted [phosphopurine] -fragment ions. We propose and discuss a potential mechanism for generation of rearranged [phosphopurine] -and complementary y-B type product ions.

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More Than Charged Base Loss — Revisiting the Fragmentation of Highly Charged Oligonucleotides

Cited by 8 publications

References 42 publications

Charge-State-Dependent Collision-Induced Dissociation Behaviors of RNA Oligonucleotides via High-Resolution Mass Spectrometry

Charge-State-Dependent Collision-Induced Dissociation Behaviors of RNA Oligonucleotides via High-Resolution Mass Spectrometry

Mass spectrometry of modified RNAs: recent developments

DNA Oligonucleotide Fragment Ion Rearrangements Upon Collision-Induced Dissociation

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