Evidence map›Paper›PMID 33453165›Full record

ArticleMolecular cell2021

Computationally reconstructing cotranscriptional RNA folding from experimental data reveals rearrangement of non-native folding intermediates.

Angela M Yu, Paul M Gasper, Luyi Cheng, Lien B Lai, Simi Kaur, Venkat Gopalan, Alan A Chen, Julius B Lucks

Open access · greenAbstract read
In one paragraph

Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
5.9field-weighted citation impact, top 3% of its field
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

43 citing papers in PubMed, 89 citations in OpenAlex.

  1. Article
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  7. CAR-SPLASH identifies nascent pre-mRNA structures implicated in kinetic coupling and alternative splicing.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  8. Article
  9. Article
  10. Computational modeling of cotranscriptional RNA folding.Computational and structural biotechnology journal · 2025
    Review
  11. Article
  12. Article
  13. Article
  14. Co-transcriptional gene regulation in eukaryotes and prokaryotes.Nature reviews. Molecular cell biology · 2024
    Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Tailor made: the art of therapeutic mRNA design.Nature reviews. Drug discovery · 2024
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 1 country.

Angela M YuTri-Institutional Program in Computational Biology and Medicine, Weill Cornell Medicine, New York, NY 10065, USA; Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60201, USA.
Paul M GasperDepartment of Chemistry and the RNA Institute, University at Albany, Albany, NY 12222, USA.
Luyi ChengInterdisciplinary Biological Sciences Graduate Program, Northwestern University, Evanston, IL 60201, USA.
Lien B LaiDepartment of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
Simi KaurDepartment of Chemistry and the RNA Institute, University at Albany, Albany, NY 12222, USA.
Venkat GopalanDepartment of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
Alan A ChenDepartment of Chemistry and the RNA Institute, University at Albany, Albany, NY 12222, USA. Electronic address: achen6@albany.edu.
Julius B LucksDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60201, USA. Electronic address: jblucks@northwestern.edu.
University at Albany, State University of New York · USNorthwestern University · USThe Ohio State University · USCornell University · US

Funding

Tri-Institutional Training Program in Computational Biology & MedicineT32GM083937 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHRISTINI, DAVID J. · 2009 to 2018
$3.1M
A New High-Throughput Technology To Reveal The Dynamic Functional States of RNAsDP2GM110838 · NIGMS · NORTHWESTERN UNIVERSITY · PI LUCKS, JULIUS BEAU · 2013 to 2013
$2.1M
Dissecting functional cooperation among subunits in a catalytic ribonucleoproteinR01GM120582 · NIGMS · OHIO STATE UNIVERSITY · PI GOPALAN, VENKAT · 2016 to 2019
$1.9M
Functional Roles of Nascent RNA Structure in Regulating and Coordinating Gene Expression - supplementR01GM130901 · NIGMS · NORTHWESTERN UNIVERSITY · PI LUCKS, JULIUS BEAU · 2020 to 2023
$1.2M
Typhoon FLA9500 Biomedical ImagerS10OD023582 · OD · OHIO STATE UNIVERSITY · PI JACKMAN, JANE ELIZABETH · 2017 to 2017
$144k
NIGMS NIH HHS DP2 GM110838NIGMS NIH HHS R01 GM120582NIGMS NIH HHS R01 GM130901NIGMS NIH HHS T32 GM083937NIH HHS S10 OD023582
6 · The paper itself

Abstract

The series of RNA folding events that occur during transcription can critically influence cellular RNA function. Here, we present reconstructing RNA dynamics from data (R2D2), a method to uncover details of cotranscriptional RNA folding. We model the folding of the Escherichia coli signal recognition particle (SRP) RNA and show that it requires specific local structural fluctuations within a key hairpin to engender efficient cotranscriptional conformational rearrangement into the functional structure. All-atom molecular dynamics simulations suggest that this rearrangement proceeds through an internal toehold-mediated strand-displacement mechanism, which can be disrupted with a point mutation that limits local structural fluctuations and rescued with compensating mutations that restore these fluctuations. Moreover, a cotranscriptional folding intermediate could be cleaved in vitro by recombinant E. coli RNase P, suggesting potential cotranscriptional processing. These results from experiment-guided multi-scale modeling demonstrate that even an RNA with a simple functional structure can undergo complex folding and processing during synthesis.

Indexed as

RNA FoldingEscherichia coliEscherichia coli ProteinsRibonuclease PRNA, BacterialSignal Recognition ParticleEscherichia coli ProteinsRibonuclease PRNA, BacterialSignal Recognition Particlecotranscriptional RNA foldingmolecular dynamicsRNARNA fluctuationsRNA folding dynamicsRNA structureSHAPE-seqsignal recognition particletoehold strand displacementtranscription

Identifiers

PMID33453165
PMCPMC8061711
OpenAlexW3118787591

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.