Systems NMR: single-sample quantification of RNA, proteins and metabolites for biomolecular network analysis
Open accessAbstract
Cellular behavior is controlled by the interplay of diverse biomolecules. Most experimental methods, however, can only monitor a single molecule class or reaction type at a time. We developed an in vitro nuclear magnetic resonance spectroscopy (NMR) approach, which permitted dynamic quantification of an entire 'heterotypic' network-simultaneously monitoring three distinct molecule classes (metabolites, proteins and RNA) and all elementary reaction types (bimolecular interactions, catalysis, unimolecular changes). Focusing on an eight-reaction co-transcriptional RNA folding network, in a single sample we recorded over 35 time points with over 170 observables each, and accurately determined five core reaction constants in multiplex. This reconstruction revealed unexpected cross-talk between the different reactions. We further observed dynamic phase-separation in a system of five distinct RNA-binding domains in the course of the RNA transcription reaction. Our Systems NMR approach provides a deeper understanding of biological network dynamics by combining the dynamic resolution of biochemical assays and the multiplexing ability of 'omics'.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
NMR spectroscopy has a long-standing history of being used to effectively detect and measure a wide range of protein-ligand interactions, applicable in high-throughput fashion.
“An example of the employment of NMR in functional analysis is the detection of protein–metabolite interactions, in fact NMR spectroscopy has a long-standing history of being used to effectively detect and measure a wide range of protein–ligand interactions,144–146 which is also applicable in a high-throughput fashion.”
From Connecting metabolome and phenotype: recent advances in functional metabolomics tools for the identification of bioactive natural products (2024) · cites this paper as [145]
The Introduction describes NMR as commonly used to monitor reactions, and the Discussion (NMR assay limits; page unavailable) says it can quantify bimolecular binding and suggests that a few dozen protein-focused reactions could be observed in parallel. This supports quantitative interaction analysis and potential multiplexing, but does not establish a long-standing history of high-throughput detection across a wide range of protein–ligand interactions. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 72 · Cited by 20
Research works printed but not linked: 1
- [69]Cavanagh Protein NMR Spectroscopy: Principles and Practice. Ch 1.4 New York Academic Press 1996
- Authors
- Nikolaev, Y., Ripin, N., Soste, M., Picotti, P., Iber, D., & Allain, F. H.-T.
- Affiliations
- ETH Zurich (CH)
- Corresponding author
- Nikolaev, Yaroslav
- Allain, Frédéric H.-T.
- Venue
- Nature Methods
- Published
- 2019-07-29
- Volume
- 16
- Issue
- 8
- Pages
- 743-749
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- PMC
- PMC6837886
- OpenAlex
- W2966541398
- Cited by
- 20
- References
- 72
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 1
- FWCI
- 1.20
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-08-12)
- Open access
- bronze
- doi.org
- Locations
- Nature Methods (publishedVersion)
- PubMed (publishedVersion)
- Repository for Publications and Research Data (ETH Zurich) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ETH Zürich Research Collection
- Funders
- National Science Foundation
- Novartis Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Promedica Stiftung (1300/M)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced NMR Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- multiplexed quantification, RNA folding, RNA-binding domain, phase separation, reaction kinetics, biomolecular networks, metabolites, proteins, RNA, transcription
- MeSH terms
- Humans, Nucleic Acid Conformation, Protein Conformation, Proteins, RNA, Nuclear Magnetic Resonance, Biomolecular, Gene Regulatory Networks, Metabolome, HEK293 Cells, RNA Folding
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
