Evidence map›Paper›PMID 28232751›Full record

ArticleNature communications2017

CLK-dependent exon recognition and conjoined gene formation revealed with a novel small molecule inhibitor.

Tyler Funnell, Shinya Tasaki, Arusha Oloumi, Shinsuke Araki, Esther Kong, Damian Yap, Yusuke Nakayama, Christopher S Hughes, S-W Grace Cheng, Hirokazu Tozaki and 26 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
6.6field-weighted citation impact, top 2% 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

33 citing papers in PubMed, 136 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. RNA Splicing as a Therapeutic Target in Cancer.Annual review of pharmacology and toxicology · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Research towards selective inhibition of the CLK3 kinase.Beilstein journal of organic chemistry · 2025
    Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Microbiology spectrum · 2022
    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

36 authors at 4 institutions in 3 countries.

Tyler FunnellDepartment of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada, V5Z 1L3.
Shinya TasakiPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Arusha OloumiDepartment of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada, V5Z 1L3.
Shinsuke ArakiPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Esther KongDepartment of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada, V5Z 1L3.
Damian YapDepartment of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada, V5Z 1L3.ORCID 0000-0002-5370-4592
Yusuke NakayamaPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Christopher S HughesMichael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada, V5Z 1L3.ORCID 0000-0002-6980-4459
S-W Grace ChengMichael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada, V5Z 1L3.
Hirokazu TozakiPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Misa IwataniPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Satoshi SasakiPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Tomohiro OhashiPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Tohru MiyazakiPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Nao MorishitaPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Daisuke MorishitaPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Mari Ogasawara-ShimizuPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Momoko OhoriPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Shoichi NakaoPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Masatoshi KarashimaPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Masaya SanoPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Aiko MuraiPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Toshiyuki NomuraPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Noriko UchiyamaPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Tomohiro KawamotoPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Ryujiro HaraPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Osamu NakanishiPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Karey ShumanskyDepartment of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada, V5Z 1L3.
Jamie RosnerDepartment of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada, V5Z 1L3.
Adrian WanDepartment of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada, V5Z 1L3.
Steven McKinneyDepartment of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada, V5Z 1L3.
Gregg B MorinMichael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada, V5Z 1L3.
Atsushi NakanishiPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
Sohrab ShahDepartment of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada, V5Z 1L3.
Hiroyoshi ToyoshibaPharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan. hiroyoshi.toyoshiba@takeda.com.
Samuel AparicioDepartment of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada, V5Z 1L3. saparicio@bccrc.ca.
Takeda (Japan) · JPBC Cancer Agency · CAFujirebio (Japan) · JPJapan Agency for Medical Research and Development · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

CDC-like kinase phosphorylation of serine/arginine-rich proteins is central to RNA splicing reactions. Yet, the genomic network of CDC-like kinase-dependent RNA processing events remains poorly defined. Here, we explore the connectivity of genomic CDC-like kinase splicing functions by applying graduated, short-exposure, pharmacological CDC-like kinase inhibition using a novel small molecule (T3) with very high potency, selectivity, and cell-based stability. Using RNA-Seq, we define CDC-like kinase-responsive alternative splicing events, the large majority of which monotonically increase or decrease with increasing CDC-like kinase inhibition. We show that distinct RNA-binding motifs are associated with T3 response in skipped exons. Unexpectedly, we observe dose-dependent conjoined gene transcription, which is associated with motif enrichment in the last and second exons of upstream and downstream partners, respectively. siRNA knockdown of CLK2-associated genes significantly increases conjoined gene formation. Collectively, our results reveal an unexpected role for CDC-like kinase in conjoined gene formation, via regulation of 3'-end processing and associated splicing factors.The phosphorylation of serine/arginine-rich proteins by CDC-like kinase is a central regulatory mechanism for RNA splicing reactions. Here, the authors synthesize a novel small molecule CLK inhibitor and map CLK-responsive alternative splicing events and discover an effect on conjoined gene transcription.

Indexed as

Alternative SplicingExonsGene Expression ProfilingGenome, HumanHCT116 CellsHumansImidazolesPhosphorylationProtein Kinase InhibitorsProtein Serine-Threonine KinasesProtein-Tyrosine KinasesPyrimidinesRNA-Binding ProteinsRNA, MessengerRNA, Small InterferingStructure-Activity RelationshipClk dual-specificity kinasesImidazolesProtein Kinase InhibitorsProtein Serine-Threonine KinasesProtein-Tyrosine KinasesPyrimidinesRNA-Binding ProteinsRNA, MessengerRNA, Small Interfering

Identifiers

PMID28232751
PMCPMC5431906
OpenAlexW2589109655

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.