ArticleNature2014
Genome-wide probing of RNA structure reveals active unfolding of mRNA structures in vivo.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 556 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
556 citing papers in PubMed, 1 synthesis or guideline pooled it, 914 citations in OpenAlex.
- The genetic and biochemical determinants of mRNA degradation rates in mammals.Genome biology · 2022Pooled it
- Key Points to Consider When Studying RNA Remodeling by Proteins.Methods in molecular biology (Clifton, N.J.) · 2027Review
- Structure-driven function of plant lncRNAs: conserved RNA architectures in transcriptional and post-transcriptional regulation.RNA biology · 2026Review
- mRNA Structure Regulates Translation at Every Step.Biochemistry · 2026Review
- dsRNAscan maps human dsRNAome, revealing conservation, intermolecular dsRNA, and correlates of ADAR dependency.Molecular cell · 2026Article
- Multiomic proximity labeling in vivo by D-amino-acid-activated peroxidase reaction.Nature chemical biology · 2026Article
- FAST-MaP: Chemical Mapping of RNA Structures Using Primer-less Sequencing.bioRxiv : the preprint server for biology · 2026Article
- Maintaining transcriptome solubility constrains mRNA sequence composition.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A passive protein environment offsets RNA folding energetics in cells.bioRxiv : the preprint server for biology · 2026Article
- Modtector: ultra-fast modification signal mining on mapped sequencing reads.Bioinformatics (Oxford, England) · 2026Article
- Advances in Poultry RNA-Omics Research: Technologies, RNA Information Layers, and Applications in Complex Traits.Animals : an open access journal from MDPI · 2026Review
- Folding the message: mRNA structure as a regulatory layer of human mitochondrial gene expression.Biochimica et biophysica acta. Molecular cell research · 2026Review
- DMS-MaPseq and DREEM Analyses Implicate the Critical Role of RNA Structural Dynamics in Turnip Yellow Mosaic Virus Pathogenicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Direct detection of alternative DNA conformations with long-read sequencing and machine learning approaches.bioRxiv : the preprint server for biology · 2026Article
- Protein crowders remodel RNA electrostatics, hydration, and dynamics: a challenge to steric crowding models.Nucleic acids research · 2026Article
- seq2ribo: structure-aware integration of machine learning and simulation to predict ribosome location profiles from RNA sequences.Bioinformatics (Oxford, England) · 2026Article
- RNA regulation in plants.Science China. Life sciences · 2026Review
- Bridging technical innovation and computational advances in studies of RNA-protein assemblies.Nature reviews. Genetics · 2026Review
- Identification of conserved RNA regulatory switches in living cells using RNA secondary structure ensemble mapping and covariation analysis.Nature biotechnology · 2026Article
- FIRST-seq: a nanopore-based cDNA sequencing platform for RNA modification and structure profiling.Genome biology · 2026Article
496 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
RNA has a dual role as an informational molecule and a direct effector of biological tasks. The latter function is enabled by RNA's ability to adopt complex secondary and tertiary folds and thus has motivated extensive computational and experimental efforts for determining RNA structures. Existing approaches for evaluating RNA structure have been largely limited to in vitro systems, yet the thermodynamic forces which drive RNA folding in vitro may not be sufficient to predict stable RNA structures in vivo. Indeed, the presence of RNA-binding proteins and ATP-dependent helicases can influence which structures are present inside cells. Here we present an approach for globally monitoring RNA structure in native conditions in vivo with single-nucleotide precision. This method is based on in vivo modification with dimethyl sulphate (DMS), which reacts with unpaired adenine and cytosine residues, followed by deep sequencing to monitor modifications. Our data from yeast and mammalian cells are in excellent agreement with known messenger RNA structures and with the high-resolution crystal structure of the Saccharomyces cerevisiae ribosome. Comparison between in vivo and in vitro data reveals that in rapidly dividing cells there are vastly fewer structured mRNA regions in vivo than in vitro. Even thermostable RNA structures are often denatured in cells, highlighting the importance of cellular processes in regulating RNA structure. Indeed, analysis of mRNA structure under ATP-depleted conditions in yeast shows that energy-dependent processes strongly contribute to the predominantly unfolded state of mRNAs inside cells. Our studies broadly enable the functional analysis of physiological RNA structures and reveal that, in contrast to the Anfinsen view of protein folding whereby the structure formed is the most thermodynamically favourable, thermodynamics have an incomplete role in determining mRNA structure in vivo.
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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.