ArticleJournal of the American Chemical Society2015
Bidirectional Direct Sequencing of Noncanonical RNA by Two-Dimensional Analysis of Mass Chromatograms.
Article in Journal of the American Chemical Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- De novo direct sequencing of small therapeutic RNAs by layer-by-layer intensity-resolved mass spectrometry.Nucleic acids research · 2026Article
- A cholesterol-responsive hepatic tRNA-derived small RNA regulates cholesterol homeostasis and atherosclerosis development.Nature communications · 2025Article
- tRNA modifications: greasing the wheels of translation and beyond.RNA biology · 2025Review
- Mass Spectrometry-Based Direct Sequencing of tRNAs De Novo and Quantitative Mapping of Multiple RNA Modifications.Journal of the American Chemical Society · 2024Article
- Advances in methods for tRNA sequencing and quantification.Trends in genetics : TIG · 2024Review
- tRNA renovatio: Rebirth through fragmentation.Molecular cell · 2023Review
- Trivalent rare earth metal cofactors confer rapid NP-DNA polymerase activity.Science (New York, N.Y.) · 2023Article
- Challenges and emerging trends in liquid chromatography-based analyses of mRNA pharmaceuticals.Journal of pharmaceutical and biomedical analysis · 2023Review
- Exploring the expanding universe of small RNAs.Nature cell biology · 2022Review
- Locating chemical modifications in RNA sequences through ribonucleases and LC-MS based analysis.Methods in enzymology · 2021Article
- Naturally occurring modified ribonucleosides.Wiley interdisciplinary reviews. RNA · 2020Review
- 2D-HELS MS Seq: A General LC-MS-Based Method for Direct and de novo Sequencing of RNA Mixtures with Different Nucleotide Modifications.Journal of visualized experiments : JoVE · 2020Article
- Direct Sequencing of tRNA by 2D-HELS-AA MS Seq Reveals Its Different Isoforms and Dynamic Base Modifications.ACS chemical biology · 2020Article
- Broadly applicable oligonucleotide mass spectrometry for the analysis of RNA writers and erasers in vitro.Nucleic acids research · 2020Article
- Synthesis of phosphoramidate-linked DNA by a modified DNA polymerase.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- A general LC-MS-based RNA sequencing method for direct analysis of multiple-base modifications in RNA mixtures.Nucleic acids research · 2019Article
- Going global: the new era of mapping modifications in RNA.Wiley interdisciplinary reviews. RNA · 2017Review
- Pinpointing RNA-Protein Cross-Links with Site-Specific Stable Isotope-Labeled Oligonucleotides.Journal of the American Chemical Society · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mass spectrometry (MS) is a powerful technique for characterizing noncanonical nucleobases and other chemical modifications in small RNAs, yielding rich chemical information that is complementary to high-throughput indirect sequencing. However, mass spectra are often prohibitively complex when fragment ions are analyzed following either solution phase hydrolysis or gas phase fragmentation. For all but the simplest cases, ions arising from multiple fragmentation events, alternative fragmentation pathways, and diverse salt adducts frequently obscure desired single-cut fragment ions. Here we show that it is possible to take advantage of predictable regularities in liquid chromatographic (LC) separation of optimized RNA digests to greatly simplify the interpretation of complex MS data. A two-dimensional analysis of extracted compound chromatograms permits straightforward and robust de novo sequencing, using a novel Monte Carlo algorithm that automatically generates bidirectional paired-end reads, pinpointing the position of modified nucleotides in a sequence. We demonstrate that these advances permit routine LC-MS sequencing of RNAs containing noncanonical nucleotides, and we furthermore examine the applicability of this approach to the study of oligonucleotides containing artificial modifications as well as those commonly observed in post-transcriptionally modified RNAs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.