Evidence map›Paper›PMID 38714659›Full record

ArticleNature communications2024

CRISPR-dCas13d-based deep screening of proximal and distal splicing-regulatory elements.

Yocelyn Recinos, Dmytro Ustianenko, Yow-Tyng Yeh, Xiaojian Wang, Martin Jacko, Lekha V Yesantharao, Qiyang Wu, Chaolin Zhang

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing 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

22 citing papers in PubMed.

  1. Article
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  11. Article
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  16. Article
  17. Review
  18. A Manual for Genome and Transcriptome Engineering.IEEE reviews in biomedical engineering · 2025
    Review
  19. Review
  20. Strategies for programmable manipulation of alternative splicing.Current opinion in genetics & development · 2024
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Yocelyn RecinosDepartment of Systems Biology, Columbia University, New York, NY, 10032, USA.
Dmytro UstianenkoDepartment of Systems Biology, Columbia University, New York, NY, 10032, USA.
Yow-Tyng YehDepartment of Systems Biology, Columbia University, New York, NY, 10032, USA.
Xiaojian WangDepartment of Systems Biology, Columbia University, New York, NY, 10032, USA.
Martin JackoDepartment of Systems Biology, Columbia University, New York, NY, 10032, USA.
Lekha V YesantharaoDepartment of Systems Biology, Columbia University, New York, NY, 10032, USA.
Qiyang WuDepartment of Systems Biology, Columbia University, New York, NY, 10032, USA.
Chaolin ZhangDepartment of Systems Biology, Columbia University, New York, NY, 10032, USA. cz2294@columbia.edu.ORCID http://orcid.org/0000-0002-8310-7537

Funding

Complexity and evolution of splicing-regulatory networksR35GM145279 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Chaolin Zhang · 2022 to 2026
$4.6M
Mapping proximal and distal splicing-regulatory elementsR01HG012359 · NHGRI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Chaolin Zhang · 2023 to 2026
$2.4M
BD Biosciences InfluxS10OD020056 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SNOECK, HANS-WILLEM E · 2015 to 2015
$600k
Mapping proximal and distal splicing-regulatory elementsR56HG012359 · NHGRI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ZHANG, CHAOLIN · 2022 to 2022
$569k
Becton Dickinson LSR II Analytical Flow CytometerS10RR027050 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CLYNES, RAPHAEL A. · 2011 to 2011
$413k
NCRR NIH HHS S10 RR027050NHGRI NIH HHS R01 HG012359NHGRI NIH HHS R56 HG012359NIGMS NIH HHS R35 GM145279NIH HHS S10 OD020056
6 · The paper itself

Abstract

Pre-mRNA splicing, a key process in gene expression, can be therapeutically modulated using various drug modalities, including antisense oligonucleotides (ASOs). However, determining promising targets is hampered by the challenge of systematically mapping splicing-regulatory elements (SREs) in their native sequence context. Here, we use the catalytically inactive CRISPR-RfxCas13d RNA-targeting system (dCas13d/gRNA) as a programmable platform to bind SREs and modulate splicing by competing against endogenous splicing factors. SpliceRUSH, a high-throughput screening method, was developed to map SREs in any gene of interest using a lentivirus gRNA library that tiles the genetic region, including distal intronic sequences. When applied to SMN2, a therapeutic target for spinal muscular atrophy, SpliceRUSH robustly identifies not only known SREs but also a previously unknown distal intronic SRE, which can be targeted to alter exon 7 splicing using either dCas13d/gRNA or ASOs. This technology enables a deeper understanding of splicing regulation with applications for RNA-based drug discovery.

Indexed as

CRISPR-Cas SystemsExonsIntronsRNA, Guide, CRISPR-Cas SystemsRNA SplicingSurvival of Motor Neuron 2 ProteinHEK293 CellsHumansMuscular Atrophy, SpinalOligonucleotides, AntisenseRegulatory Sequences, Nucleic AcidRNA PrecursorsOligonucleotides, AntisenseRNA, Guide, CRISPR-Cas SystemsRNA PrecursorsSMN2 protein, humanSurvival of Motor Neuron 2 Protein

Identifiers

PMID38714659
PMCPMC11076525

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.