ArticleCancer cell2019
Therapeutic Targeting of RNA Splicing Catalysis through Inhibition of Protein Arginine Methylation.
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Article in Cancer cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers.
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172citing papers in PubMed
11.5field-weighted citation impact, top 1% of its field
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Who cites it
172 citing papers in PubMed, 276 citations in OpenAlex.
- Serine Starvation Modulates mRNA Splicing through Translational Inhibition of SRSF Proteins.Cancer research · 2026Article
- PRMT1-SFPQ regulates intron retention to control matrix gene expression during craniofacial development.eLife · 2026Article
- Targeting PRMTs with small-molecule inhibitors: a comprehensive review.RSC medicinal chemistry · 2026Review
- Deconvoluting the multi-faceted roles of alternative splicing events in cancer: From underlying mechanisms to innovative therapeutics.Acta pharmaceutica Sinica. B · 2026Review
- Reprogramming resistance in advanced lung cancer: epigenetic modulation to restore therapeutic vulnerability.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Targeting PRMT5 Inhibitor-Induced Adaptation in Pancreatic Cancer with the RBM39 Degrader Indisulam.Cancer research communications · 2026Article
- Review
- PRMT5 promotes psoriatic inflammation through mediating dimethylation of p65 in keratinocytes.Molecular medicine (Cambridge, Mass.) · 2026Article
- Arginine Methylation in Alternative Splicing: Implications for Cancer Therapy.Journal of cellular physiology · 2026Review
- Review
- PRMT1 facilitates the tumorigenesis of chronic lymphocytic leukemia by regulating methylation of MAST1.Leukemia · 2026Article
- A synergistic interaction between PRMT5 and LSD1 inhibitors in AML.Science advances · 2026Article
- Targeting intracellular mRNA mJournal of advanced research · 2026Review
- Pharmacological perturbation of splicing elicits SMG1 reduction: Implications for cancer therapy.iScience · 2026Article
- Article
- BCLAF1 links RNA splicing to ATF4-dependent metabolic adaptation in acute myeloid leukemia.bioRxiv : the preprint server for biology · 2026Article
- Sequence-dependent splicing dysregulation drives therapy resistance in pediatric AML.Cell reports. Medicine · 2026Article
- Unlocking the undruggable spliceosome: generative AI and structural dynamics in cancer therapy.Frontiers in cell and developmental biology · 2026Review
- Targeting the PRMT1 axis in cancer: from epigenetic plasticity to contextual therapeutic interventions.Frontiers in oncology · 2026Review
- RNA Splicing as a Therapeutic Target in Cancer.Annual review of pharmacology and toxicology · 2026Review
112 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
35 authors at 9 institutions in 5 countries.
Jia Yi FongInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 119077, Singapore.
Luca PignataInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore.
Pierre-Alexis GoyInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore.
Kimihito Cojin KawabataDepartments of Medicine and Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA.
Stanley Chun-Wei LeeHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Cheryl M KohInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore.
Daniele MusianiDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20146 Milan, Italy.
Enrico MassignaniDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20146 Milan, Italy.
Andriana G KotiniDepartment of Oncological Sciences and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Alex PensonHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Cheng Mun WunInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore.
Yudao ShenMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Megan SchwarzDepartment of Oncological Sciences and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Diana Hp LowInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore.
Alexander RialdiDepartment of Oncological Sciences and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Michelle KiHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Heike WollmannInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore.
Slim MzoughiInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore.
Florence GayInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore.
Christine ThompsonEpigenetics Research Unit, GlaxoSmithKline, Collegeville, PA 19426, USA.
Timothy HartEpigenetics Research Unit, GlaxoSmithKline, Collegeville, PA 19426, USA.
Olena BarbashEpigenetics Research Unit, GlaxoSmithKline, Collegeville, PA 19426, USA.
Genna M LucianiStructural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
Magdalena M SzewczykStructural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
Bas J WoutersDivision of Hematology and Medical Oncology, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10065, USA; Department of Hematology, Erasmus University Medical Center, 3015 GD Rotterdam, Netherlands.
Ruud DelwelDepartment of Hematology, Erasmus University Medical Center, 3015 GD Rotterdam, Netherlands.
Eirini P PapapetrouDepartment of Oncological Sciences and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Dalia Barsyte-LovejoyStructural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
Cheryl H ArrowsmithStructural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada; Ontario Cancer Institute/Princess Margaret Hospital, Toronto, ON M5G 2M9, Canada.
Mark D MindenOntario Cancer Institute/Princess Margaret Hospital, Toronto, ON M5G 2M9, Canada.
Jian JinMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Ari MelnickDepartments of Medicine and Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA.
Tiziana BonaldiDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20146 Milan, Italy.
Omar Abdel-WahabHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: abdelwao@mskcc.org.
Ernesto GuccioneInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore; Department of Oncological Sciences and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pharmacological Sciences and Mount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: ernesto.guccione@mssm.edu.
Agency for Science, Technology and Research · SGIcahn School of Medicine at Mount Sinai · USMemorial Sloan Kettering Cancer Center · USCornell University · USEuropean Institute of Oncology · ITGlaxoSmithKline (United States) · USUniversity of Toronto · CAOntario Institute for Cancer Research · CAErasmus MC · NL
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MTRAINING PROGRAM IN CANCER THERAPYT32CA078207 · NCI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI James J Manfredi · 1999 to 2026
$11.6MGenetic and molecular basis for SRSF2 mutations in myelodysplasiaR01HL128239 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Omar Abdel-Wahab, Robert K Bradley · 2015 to 2026
$8.0MDeveloping and credentialing patient-derived xenograft models to advance therapeutic approaches for chronic myelomonocytic leukemiaR37CA234021 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI PADRON, ERIC · 2019 to 2025
$3.4MOrigins of BRAF-mutant hematologic malignancies and their therapeutic resistanceR01CA201247 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ABDEL-WAHAB, OMAR, PARK, CHRISTOPHER Y · 2016 to 2020
$2.7MDiscovery of Selective Inhibitors for Histone MethyltransferasesR01GM122749 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI JIN, JIAN · 2017 to 2020
$1.3MNCI NIH HHS P30 CA008748NCI NIH HHS R01 CA201247NCI NIH HHS R37 CA234021NCI NIH HHS T32 CA078207NHLBI NIH HHS R01 HL128239NIGMS NIH HHS R01 GM122749Wellcome Trust
Abstract
Cancer-associated mutations in genes encoding RNA splicing factors (SFs) commonly occur in leukemias, as well as in a variety of solid tumors, and confer dependence on wild-type splicing. These observations have led to clinical efforts to directly inhibit the spliceosome in patients with refractory leukemias. Here, we identify that inhibiting symmetric or asymmetric dimethylation of arginine, mediated by PRMT5 and type I protein arginine methyltransferases (PRMTs), respectively, reduces splicing fidelity and results in preferential killing of SF-mutant leukemias over wild-type counterparts. These data identify genetic subsets of cancer most likely to respond to PRMT inhibition, synergistic effects of combined PRMT5 and type I PRMT inhibition, and a mechanistic basis for the therapeutic efficacy of PRMT inhibition in cancer.
Indexed as
AnimalsAntineoplastic AgentsCatalysisEnzyme InhibitorsEthylenediaminesGene Expression Regulation, NeoplasticGene Regulatory NetworksHumansK562 CellsLeukemia, Myeloid, AcuteMice, Inbred C57BLMice, TransgenicProtein-Arginine N-MethyltransferasesPyrrolesRepressor ProteinsRNA, NeoplasmAntineoplastic AgentsEnzyme InhibitorsEthylenediaminesMS023 compoundPRMT1 protein, humanPRMT5 protein, humanProtein-Arginine N-MethyltransferasesPyrrolesRepressor ProteinsRNA, NeoplasmAMLArginine methylationMDSMS023PRMT1PRMT5SF3B1Splicing factor mutationsSRSF2U2AF1
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