Evidence map›Paper›PMID 39014073›Full record

ArticleNature methods2024

A systematic search for RNA structural switches across the human transcriptome.

Matvei Khoroshkin, Daniel Asarnow, Shaopu Zhou, Albertas Navickas, Aidan Winters, Jackson Goudreau, Simon K Zhou, Johnny Yu, Christina Palka, Lisa Fish and 7 more

Abstract read
In one paragraph

Article in Nature methods, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Review
  2. Design and discovery of 'tug-of-war' riboswitches.bioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Article
  5. Human Synthetic Biology and Programmable Gene Regulation Control.Annual review of genomics and human genetics · 2025
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Review
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

17 authors.

Matvei KhoroshkinDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Daniel AsarnowDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Shaopu ZhouDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Albertas NavickasDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-0016-2643
Aidan WintersDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA.
Jackson GoudreauDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Simon K ZhouSandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-8695-7943
Johnny YuDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Christina PalkaGladstone Institute of Data Science and Biotechnology, San Francisco, CA, USA.
Lisa FishDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Ashir BorahDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Kian YousefiDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Christopher CarpenterDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
K Mark AnselSandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-4840-9879
Yifan ChengDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-9535-0369
Luke A GilbertDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-5854-0825
Hani GoodarziDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA. hani.goodarzi@ucsf.edu.ORCID http://orcid.org/0000-0002-9648-8949

Funding

Molecular and Cellular Mechanisms in CancerT32CA108462 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOGA, ANDREI · 2004 to 2024
$10.4M
An antisense RNA-mediated regulatory program that drives cancer metastasisR01CA240984 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOODARZI, HANI · 2019 to 2023
$2.5M
A GENETIC INTERACTION MAP OF THE HUMAN NUCLEUSDP2CA239597 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GILBERT, LUKE · 2018 to 2018
$2.4M
Advancing cryo-EM technology to address difficult biological questionsR35GM140847 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Yifan Cheng · 2021 to 2026
$2.1M
Acquisition of an electron microscope for high-resolution single particle cryo-EMS10OD021741 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2016 to 2016
$2.0M
Glacios™ Cryo Transmission Electron Microscope with 200 kV XFEG opticsS10OD026881 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2019 to 2019
$1.8M
The RNA structural code underlying pathological regulation of RNA splicing in metastasisR01CA244634 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOODARZI, HANI · 2021 to 2025
$1.8M
Molecular Biophysics Training GrantT32GM149436 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Aashish Manglik · 2023 to 2026
$1.6M
Illumina NovaSeq 6000 Sequencing SystemS10OD028511 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHOW, ERIC D · 2020 to 2020
$583k
Linux cluster for near atomic resolution single particle cryo-EMS10OD020054 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2015 to 2015
$456k
NCI NIH HHS DP2 CA239597NCI NIH HHS R01 CA240984NCI NIH HHS R01 CA244634NCI NIH HHS T32 CA108462NIGMS NIH HHS R35 GM140847NIGMS NIH HHS T32 GM149436NIH HHS S10 OD020054NIH HHS S10 OD021741NIH HHS S10 OD026881NIH HHS S10 OD028511
6 · The paper itself

Abstract

RNA structural switches are key regulators of gene expression in bacteria, but their characterization in Metazoa remains limited. Here, we present SwitchSeeker, a comprehensive computational and experimental approach for systematic identification of functional RNA structural switches. We applied SwitchSeeker to the human transcriptome and identified 245 putative RNA switches. To validate our approach, we characterized a previously unknown RNA switch in the 3' untranslated region of the RORC (RAR-related orphan receptor C) transcript. In vivo dimethyl sulfate (DMS) mutational profiling with sequencing (DMS-MaPseq), coupled with cryogenic electron microscopy, confirmed its existence as two alternative structural conformations. Furthermore, we used genome-scale CRISPR screens to identify trans factors that regulate gene expression through this RNA structural switch. We found that nonsense-mediated messenger RNA decay acts on this element in a conformation-specific manner. SwitchSeeker provides an unbiased, experimentally driven method for discovering RNA structural switches that shape the eukaryotic gene expression landscape.

Indexed as

Nucleic Acid ConformationTranscriptome3' Untranslated RegionsComputational BiologyCryoelectron MicroscopyHumansNonsense Mediated mRNA DecayRNASulfuric Acid Esters3' Untranslated Regionsdimethyl sulfateRNASulfuric Acid Esters

Identifiers

PMID39014073
PMCPMC11399106

What OpenQuestion holds

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Registered trials

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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.