Evidence map›Paper›PMID 25799993›Full record

ArticleNature2015

Structural imprints in vivo decode RNA regulatory mechanisms.

Robert C Spitale, Ryan A Flynn, Qiangfeng Cliff Zhang, Pete Crisalli, Byron Lee, Jong-Wha Jung, Hannes Y Kuchelmeister, Pedro J Batista, Eduardo A Torre, Eric T Kool and 1 more

Erratum issuedAbstract read
In one paragraph

Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 467 papers.

0numbers the graph read from it
0cells of the map it votes in
467citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

467 citing papers in PubMed.

  1. Review
  2. Article
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  5. Review
  6. Article
  7. A nucleic acid labeling chemistry reveals surface DNA on exosomes.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  8. Article
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  10. mNature communications · 2026
    Article
  11. Review
  12. Review
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  15. Article
  16. Review
  17. Review
  18. Article
  19. Optimized tRNA structure-seq reveals robust tRNA secondary structures inbioRxiv : the preprint server for biology · 2026
    Article
  20. Article

407 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Robert C SpitaleHoward Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Ryan A FlynnHoward Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Qiangfeng Cliff ZhangHoward Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Pete CrisalliDepartment of Chemistry, Stanford University, Stanford, California 94305, USA.
Byron LeeHoward Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Jong-Wha JungDepartment of Chemistry, Stanford University, Stanford, California 94305, USA.
Hannes Y KuchelmeisterDepartment of Chemistry, Stanford University, Stanford, California 94305, USA.
Pedro J BatistaHoward Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Eduardo A TorreHoward Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Eric T KoolDepartment of Chemistry, Stanford University, Stanford, California 94305, USA.
Howard Y ChangHoward Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.

Funding

Leveraging innovative technologies in basic and clinical cancer researchT32CA009302 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI, Aaron M Newman · 1985 to 2026
$19.1M
Special EquipmentP50HG007735 · NHGRI · STANFORD UNIVERSITY · PI GREENLEAF, WILLIAM JAMES · 2014 to 2018
$15.2M
Postgraduate Training Program in Epithelial BiologyT32AR007422 · NIAMS · STANFORD UNIVERSITY · PI PAUL KHAVARI · 1986 to 2026
$5.0M
Structural Motifs in RNAR01HG004361 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2007 to 2018
$4.7M
Templated Chemistry for RNA AnalysisR01GM068122 · NIGMS · STANFORD UNIVERSITY · PI KOOL, ERIC T. · 2003 to 2016
$3.5M
CONTROL OF TRANSCRIPTION BY THE 7SK RNA IN BREAST CANCERF30CA189514 · NCI · STANFORD UNIVERSITY · PI FLYNN, RYAN ALEXANDER · 2014 to 2015
$96k
Howard Hughes Medical InstituteNCI NIH HHS F30 CA189514NCI NIH HHS F30CA189514NCI NIH HHS T32 CA009302NHGRI NIH HHS P50 HG007735NHGRI NIH HHS P50HG007735NHGRI NIH HHS R01 HG004361NHGRI NIH HHS R01HG004361NIAMS NIH HHS T32AR007422NIGMS NIH HHS R01 GM068122
6 · The paper itself

Abstract

Visualizing the physical basis for molecular behaviour inside living cells is a great challenge for biology. RNAs are central to biological regulation, and the ability of RNA to adopt specific structures intimately controls every step of the gene expression program. However, our understanding of physiological RNA structures is limited; current in vivo RNA structure profiles include only two of the four nucleotides that make up RNA. Here we present a novel biochemical approach, in vivo click selective 2'-hydroxyl acylation and profiling experiment (icSHAPE), which enables the first global view, to our knowledge, of RNA secondary structures in living cells for all four bases. icSHAPE of the mouse embryonic stem cell transcriptome versus purified RNA folded in vitro shows that the structural dynamics of RNA in the cellular environment distinguish different classes of RNAs and regulatory elements. Structural signatures at translational start sites and ribosome pause sites are conserved from in vitro conditions, suggesting that these RNA elements are programmed by sequence. In contrast, focal structural rearrangements in vivo reveal precise interfaces of RNA with RNA-binding proteins or RNA-modification sites that are consistent with atomic-resolution structural data. Such dynamic structural footprints enable accurate prediction of RNA-protein interactions and N(6)-methyladenosine (m(6)A) modification genome wide. These results open the door for structural genomics of RNA in living cells and reveal key physiological structures controlling gene expression.

Indexed as

Gene Expression RegulationNucleic Acid ConformationAcylationAdenosineAnimalsBinding SitesCell SurvivalClick ChemistryComputational BiologyEmbryonic Stem CellsGenomeMiceModels, MolecularProtein BiosynthesisRegulatory Sequences, Ribonucleic AcidRibosomesAdenosineN-methyladenosineRegulatory Sequences, Ribonucleic AcidRNARNA-Binding Proteins

Identifiers

PMID25799993
PMCPMC4376618

What OpenQuestion holds

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Registered trials

None linked

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.