ArticleDevelopmental cell2020
Aberrant Expression of a Non-muscle RBFOX2 Isoform Triggers Cardiac Conduction Defects in Myotonic Dystrophy.
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Article in Developmental cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 48 citations in OpenAlex.
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- Progressive cardiac phenotypes and reduced reversibility from long-term CUGexp RNA expression in a DM1 mouse model.JCI insight · 2026Article
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- Aberrant Splicing ofCirculation. Genomic and precision medicine · 2026Article
- Ancestral intronic splicing regulatory elements in the SCNbioRxiv : the preprint server for biology · 2026Article
- Molecular genetics of myotonic dystrophy and the evolution of therapeutic approaches.Journal of human genetics · 2025Review
- The Rbfox1/LASR complex controls alternative pre-mRNA splicing by recognition of multipart RNA regulatory modules.Genes & development · 2025Article
- ESRP2-microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation.Genes & development · 2025Article
- Functions of the Muscleblind-like protein family and their role in disease.Cell communication and signaling : CCS · 2025Review
- Altered drug metabolism and increased susceptibility to fatty liver disease in a mouse model of myotonic dystrophy.Nature communications · 2024Article
- RNA splicing factor RBFOX2 is a key factor in the progression of cancer and cardiomyopathy.Clinical and translational medicine · 2024Review
- RNA-binding proteins in cardiovascular biology and disease: the beat goes on.Nature reviews. Cardiology · 2024Review
- Afterdischarges in myotonic dystrophy type 1.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Splicing regulation of GFPT1 muscle-specific isoform and its roles in glucose metabolisms and neuromuscular junction.iScience · 2023Article
- Dysregulated Rbfox2 produces aberrant splicing of CaCardiovascular diabetology · 2023Article
- The discovery, function, and regulation of epithelial splicing regulatory proteins (ESRP) 1 and 2.Biochemical Society transactions · 2023Article
- Proteomic cardiovascular risk assessment in chronic kidney disease.European heart journal · 2023Article
- Post-Transcriptional Modification by Alternative Splicing and Pathogenic Splicing Variants in Cardiovascular Development and Congenital Heart Defects.International journal of molecular sciences · 2023Review
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Authors and funding
14 authors at 3 institutions in 1 country.
Chaitali MisraDepartment of Biochemistry, University of Illinois, Urbana-Champaign, Urbana, IL, USA.
Sushant BangruDepartment of Biochemistry, University of Illinois, Urbana-Champaign, Urbana, IL, USA; Cancer Center at Illinois, University of Illinois, Urbana-Champaign, Urbana, IL, USA.
Feikai LinDepartment of Biochemistry, University of Illinois, Urbana-Champaign, Urbana, IL, USA.
Kin LamDepartment of Physics, University of Illinois, Urbana-Champaign, Urbana, IL, USA; Centers for Macromolecular Modeling, Bioinformatics and Experimental Molecular Imaging at Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana-Champaign, Urbana, IL, USA.
Sara N KoenigDepartment of Physiology and Cell Biology, Davis Heart and Lung Research Institute, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
Ellen R LubbersDepartment of Physiology and Cell Biology, Davis Heart and Lung Research Institute, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
Jamila HedhliDepartment of Bioengineering, University of Illinois, Urbana-Champaign, Urbana, IL, USA; Centers for Macromolecular Modeling, Bioinformatics and Experimental Molecular Imaging at Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana-Champaign, Urbana, IL, USA.
Nathaniel P MurphyDepartment of Physiology and Cell Biology, Davis Heart and Lung Research Institute, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
Darren J ParkerDepartment of Biochemistry, University of Illinois, Urbana-Champaign, Urbana, IL, USA.
Lawrence W DobruckiDepartment of Bioengineering, University of Illinois, Urbana-Champaign, Urbana, IL, USA; Centers for Macromolecular Modeling, Bioinformatics and Experimental Molecular Imaging at Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana-Champaign, Urbana, IL, USA; Cancer Center at Illinois, University of Illinois, Urbana-Champaign, Urbana, IL, USA.
Thomas A CooperDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.
Emad TajkhorshidDepartment of Biochemistry, University of Illinois, Urbana-Champaign, Urbana, IL, USA; Department of Physics, University of Illinois, Urbana-Champaign, Urbana, IL, USA; Department of Bioengineering, University of Illinois, Urbana-Champaign, Urbana, IL, USA; Centers for Macromolecular Modeling, Bioinformatics and Experimental Molecular Imaging at Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana-Champaign, Urbana, IL, USA; Cancer Center at Illinois, University of Illinois, Urbana-Champaign, Urbana, IL, USA.
Peter J MohlerDepartment of Physiology and Cell Biology, Davis Heart and Lung Research Institute, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
Auinash KalsotraDepartment of Biochemistry, University of Illinois, Urbana-Champaign, Urbana, IL, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois, Urbana-Champaign, Urbana, IL, USA; Cancer Center at Illinois, University of Illinois, Urbana-Champaign, Urbana, IL, USA. Electronic address: kalsotra@illinois.edu.
University of Illinois Urbana-Champaign · USThe Ohio State University Wexner Medical Center · USBaylor College of Medicine · US
Funding
WHOLE CELL SIMULATIONP41GM104601 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI SCHULTEN, KLAUS · 2012 to 2021
$19.0MMOLECULAR PATHOGENESIS OF MYOTONIC DYSTROPHYR01AR045653 · NIAMS · BAYLOR COLLEGE OF MEDICINE · PI COOPER, THOMAS A · 1999 to 2018
$8.3MDefining novel mechanisms for human arrhythmiaR35HL135754 · NHLBI · OHIO STATE UNIVERSITY · PI MOHLER, PETER J. · 2017 to 2023
$6.0MTROPONIN T ALTERNATIVE SPLICING IN EMBRYONIC HEARTR01HL045565 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI COOPER, THOMAS A · 1996 to 2018
$5.5MToolkit for High-Resolution Structure and Dynamics of Functional LipidsR01GM123455 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI MORRISSEY, JAMES H., RIENSTRA, CHAD M · 2016 to 2020
$5.0MPost-transcriptional mechanisms of gene regulation in cardiac cell growth and developmentR01HL126845 · NHLBI · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI KALSOTRA, AUINASH · 2015 to 2023
$3.5MDefining novel mechanisms for regulation of atrial INa and arrhythmiasR01HL134824 · NHLBI · OHIO STATE UNIVERSITY · PI HUND, THOMAS JEFFREY, MOHLER, PETER J. · 2017 to 2020
$3.0MTissue microenvironment (TIMe) training programT32EB019944 · NIBIB · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI BHARGAVA, ROHIT, GASKINS, REX · 2016 to 2025
$1.9MPhotochemical determination of sodium channel voltage-dependent gating and compositionR01GM122420 · NIGMS · UNIVERSITY OF IOWA · PI AHERN, CHRISTOPHER A · 2017 to 2020
$1.5MDefining the Role of Alpha II Spectrin in Cardiac Function and DiseaseF30HL137331 · NHLBI · OHIO STATE UNIVERSITY · PI LUBBERS, ELLEN · 2017 to 2020
$176kNHLBI NIH HHS F30 HL137331NHLBI NIH HHS R01 HL045565NHLBI NIH HHS R01 HL126845NHLBI NIH HHS R01 HL134824NHLBI NIH HHS R35 HL135754NIAMS NIH HHS R01 AR045653NIBIB NIH HHS T32 EB019944NIGMS NIH HHS P41 GM104601NIGMS NIH HHS R01 GM122420NIGMS NIH HHS R01 GM123455
Abstract
Myotonic dystrophy type 1 (DM1) is a multisystemic genetic disorder caused by the CTG repeat expansion in the 3'-untranslated region of DMPK gene. Heart dysfunctions occur in ∼80% of DM1 patients and are the second leading cause of DM1-related deaths. Herein, we report that upregulation of a non-muscle splice isoform of RNA-binding protein RBFOX2 in DM1 heart tissue-due to altered splicing factor and microRNA activities-induces cardiac conduction defects in DM1 individuals. Mice engineered to express the non-muscle RBFOX2
Indexed as
Action PotentialsHeart RateRNA SplicingAdultAnimalsCells, CulturedFemaleHumansMaleMice, Inbred C57BLMice, Inbred ICRMicroRNAsMiddle AgedMyocytes, CardiacMyotonic DystrophyPotassium Channels, Voltage-GatedMicroRNAsPotassium Channels, Voltage-GatedProtein IsoformsRBFOX2 protein, humanRepressor ProteinsRNA Splicing FactorsVoltage-Gated Sodium Channelsalternative splicingcardiac arrhythmiasgenome editinggenomicsion channelsmicroRNAmolecular dynamicsmyotonic dystrophyprotein-RNA interactions
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