ArticleNucleic acids research2022
Human RNase 4 improves mRNA sequence characterization by LC-MS/MS.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 45 citations in OpenAlex.
- A DNA-guided prokaryotic argonaute enables programmable RNA cleavage for sequencing and quality control ofMolecular therapy. Nucleic acids · 2026Article
- From nucleotides to intact transcripts through oligonucleotides: Integrated chromatographic strategies for therapeutic mRNA characterization.Analytical and bioanalytical chemistry · 2026Review
- Quantitative RNA modification mapping by mass spectrometry with isobaric tags and nucleobase fragment analysis.Nature communications · 2026Article
- Human 28S rRNA analysed by state-of-the-art oligonucleotide mass spectrometry: benchmarking current capabilities and a call to action for MS-Seq.bioRxiv : the preprint server for biology · 2026Article
- A nanogram-sensitive workflow for oligonucleotide mass spectrometry using ion-pair-free nanoflow HILIC and RNase benchmarking.Nucleic acids research · 2026Article
- Direct LC-HRMS/MS characterisation and RT-qPCR detection for potential mRNA-based doping agent.Analytical and bioanalytical chemistry · 2026Article
- RNase 4 improves bottom-up modification mapping ofbioRxiv : the preprint server for biology · 2026Article
- Systematic screening of archaeal MazF homologs reveals Tth-MazF1, a versatile, sequence-specific ribonuclease from Thermococcus thioreducens.Nucleic acids research · 2026Article
- Automated Online Direct mRNA Sequence Mapping Using Partial RNase T1 Digests.Analytical chemistry · 2026Article
- A single viral enzyme drives tRNA-dependent hypermodification of DNA at adenine.Nature communications · 2026Article
- Acceleration, simplification and potential parallelization of digital polymers sequencing by coupling tandem mass spectrometry with ion mobility.Nature communications · 2025Article
- Top-Down Characterization of Yeast tRNA by Gas-Phase Fractionation and Collisionally Activated Dissociation Informed by Electron Photodetachment Charge Reduction Mass Spectrometry.Analytical chemistry · 2025Article
- Characterization of intact mRNA-based therapeutics by charge detection mass spectrometry and mass photometry.Molecular therapy. Methods & clinical development · 2025Article
- Ion Mobility Gas-Phase Separation Enhances Top-Down Mass Spectrometry of Heavily Modified Guide RNA.Analytical chemistry · 2025Article
- Comprehensive nucleoside analysis of archaeal RNA modification profiles reveals an mCell reports · 2025Article
- Characterisation and analysis of mRNA critical quality attributes using liquid chromatography based methods.Journal of chromatography. A · 2025Review
- Full sequencing of 100mer sgRNA via tandem mass spectrometry by targeted RNase H digestion with customized probes.Analytical and bioanalytical chemistry · 2025Article
- Assay for ribosome stimulation of angiogenin nuclease activity.Methods in enzymology · 2025Article
- Oligonucleotide therapeutics in sports? An antidoping perspective.Archiv der Pharmazie · 2025Review
- Keeping up with a Quickly Diversifying Pharmaceutical Landscape.ACS measurement science au · 2024Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
With the rapid growth of synthetic messenger RNA (mRNA)-based therapeutics and vaccines, the development of analytical tools for characterization of long, complex RNAs has become essential. Tandem liquid chromatography-mass spectrometry (LC-MS/MS) permits direct assessment of the mRNA primary sequence and modifications thereof without conversion to cDNA or amplification. It relies upon digestion of mRNA with site-specific endoribonucleases to generate pools of short oligonucleotides that are then amenable to MS-based sequence analysis. Here, we showed that the uridine-specific human endoribonuclease hRNase 4 improves mRNA sequence coverage, in comparison with the benchmark enzyme RNase T1, by producing a larger population of uniquely mappable cleavage products. We deployed hRNase 4 to characterize mRNAs fully substituted with 1-methylpseudouridine (m1Ψ) or 5-methoxyuridine (mo5U), as well as mRNAs selectively depleted of uridine-two key strategies to reduce synthetic mRNA immunogenicity. Lastly, we demonstrated that hRNase 4 enables direct assessment of the 5' cap incorporation into in vitro transcribed mRNA. Collectively, this study highlights the power of hRNase 4 to interrogate mRNA sequence, identity, and modifications by LC-MS/MS.
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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.