Affinage

RBM20

RNA-binding protein 20 · UniProt Q5T481

Length
1227 aa
Mass
134.3 kDa
Annotated
2026-04-28
99 papers in source corpus 30 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RBM20 is a cardiac- and skeletal-muscle-enriched RNA-binding protein that functions as a master splicing repressor controlling the alternative splicing of titin and ~30 other genes critical for sarcomere mechanics, calcium handling, and ion homeostasis. RBM20 recognizes intronic UCUU motifs via its RRM domain (using a coupled folding-binding mechanism involving a C-terminal helix) and stalls the spliceosome at complex A through interactions with U1 and U2 snRNPs, thereby repressing exon inclusion in targets including TTN, CAMK2D, CACNA1C, and RYR2 (PMID:24960161, PMID:32187365, PMID:22466703). Nuclear import of RBM20 depends on Transportin-3 (TNPO3) binding to its RS/RSRSP domain, which serves as the core NLS and is phosphorylated by SR kinases (SRPK1, CLK1) and AKT2; TTN pre-mRNA nucleates RBM20 into a subnuclear splicing factory that organizes trans-chromosomal interactions to co-regulate multiple cardiac target genes (PMID:37463913, PMID:30948719, PMID:36140694). Pathogenic missense mutations in the RSRSP stretch (e.g., R636S, S639G) disrupt TNPO3 interaction and cause cytoplasmic mislocalization with formation of toxic RNP granules that drive dilated cardiomyopathy through a gain-of-function mechanism independent of splicing loss, including altered connexin-43 localization and calcium handling abnormalities (PMID:33188278, PMID:33110103, PMID:40242865, PMID:40480405).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2012 High

    The identity of the splicing factor controlling titin isoform switching in the heart was unknown; positional cloning in a rat model and human cardiac transcriptomics revealed RBM20 as the regulator of TTN and ~30 other cardiac genes, establishing it as a central cardiac splicing factor.

    Evidence Positional cloning in rat, RNA-seq of cardiac transcriptomes, cross-species validation

    PMID:22466703

    Open questions at the time
    • Full catalog of direct vs. indirect RBM20 targets not delineated
    • Mechanism of splicing repression not yet defined
  2. 2013 High

    How RBM20 achieves titin exon skipping was unclear; binding and reporter assays showed RBM20 directly binds titin pre-mRNA and accumulates on partially processed transcripts in nuclear speckle-like structures, using cooperative repression and alternative 3ʹ splice site selection.

    Evidence RNA binding assays, splice reporters, immunofluorescence in Rbm20-deficient rat

    PMID:23307558 PMID:23886709

    Open questions at the time
    • Precise RNA motif not yet identified
    • Nuclear retention mechanism not fully mapped
  3. 2014 High

    The RNA element recognized by RBM20 and the step of spliceosome assembly it blocks were unknown; CLIP-seq identified UCUU as the primary binding motif in introns flanking regulated exons, and proteomics revealed RBM20 interacts with U1/U2 snRNPs to stall the spliceosome at complex A.

    Evidence CLIP-seq, RNA-seq, quantitative proteomics in cell culture and rat/human hearts

    PMID:24960161

    Open questions at the time
    • Structural basis of UCUU recognition not resolved
    • Stoichiometry of RBM20-snRNP interaction unknown
  4. 2016 High

    Whether RBM20 influences RNA species beyond linear mRNAs was open; profiling showed RBM20 is required for biogenesis of titin I-band circular RNAs by providing the exon-skipped substrate, and cooperative regulation with RBM24 was demonstrated for ENH splicing.

    Evidence circRNA profiling in RBM20-null mice and human carriers; co-transfection/RNA-IP for ENH

    PMID:27289039 PMID:27531932

    Open questions at the time
    • Functional significance of titin circRNAs unclear
    • RBM20-RBM24 cooperativity mechanism not structurally defined
  5. 2018 High

    The physiological consequences of RBM20-dependent mis-splicing of specific targets beyond titin were unknown; loss of RBM20 shifted CAMK2D splicing toward the δ-A isoform, activating L-type Ca²⁺ current and causing Ca²⁺ overload and spontaneous SR Ca²⁺ releases, linking RBM20 directly to arrhythmogenesis.

    Evidence Rbm20 KO mice, patch-clamp electrophysiology, intracellular Ca²⁺ measurements

    PMID:29650543

    Open questions at the time
    • Contribution of individual splice targets to overall DCM phenotype not fully dissected
  6. 2018 High

    How RBM20 is directed to the nucleus and which protein domains are functionally required for splicing were open questions; the RSRSP stretch was identified as a phosphorylation-dependent NLS, and the RRM plus C-terminus were shown to be necessary and sufficient for splicing, with ZnF2 contributing to repression.

    Evidence Phospho-antibodies, S637A knock-in mouse, domain deletion splice reporters, in vitro binding

    PMID:29518215 PMID:29895960

    Open questions at the time
    • Identity of the nuclear import receptor not known
    • Kinases phosphorylating the RSRSP stretch not identified
  7. 2019 High

    Whether RBM20 organizes higher-order nuclear architecture to coordinate splicing of dispersed target genes was unknown; Hi-C and genome editing in iPSC-cardiomyocytes revealed that TTN pre-mRNA nucleates RBM20 foci forming a trans-interacting chromatin domain that brings CACNA1C and CAMK2D loci into spatial proximity.

    Evidence Hi-C, ATAC-seq, RNA-seq, CRISPR editing in human iPSC-derived cardiomyocytes

    PMID:30948919

    Open questions at the time
    • Whether the TID is required for efficient splicing or is correlative not fully established
    • Protein cofactors mediating trans-chromosomal contacts not identified
  8. 2020 High

    Whether DCM-causing RS-domain mutations act purely through loss of nuclear splicing function or also through cytoplasmic gain-of-function was debated; gene-edited pig and mouse models showed mutant RBM20 forms liquid-like cytoplasmic RNP granules, and comparative KO vs. KI mice demonstrated that cytoplasmic granule formation produces more severe disease than splicing loss alone.

    Evidence R636S knock-in pig, patient iPSC-CMs, S637A KI vs. frameshift KO mice, phase separation characterization

    PMID:33110103 PMID:33188278

    Open questions at the time
    • Molecular composition and toxicity mechanism of RNP granules not fully characterized
    • Whether granule dissolution alone is sufficient for rescue not tested
  9. 2020 High

    The atomic-level basis of RBM20's RNA specificity was unresolved; the crystal structure of the RRM bound to UCUU RNA revealed a coupled folding-binding mechanism involving a C-terminal helix encoded by exon 8, establishing how sequence-specific recognition is achieved.

    Evidence X-ray crystallography of mouse RBM20 RRM–RNA complex, mutagenesis, binding assays

    PMID:32187365

    Open questions at the time
    • Structure of full-length RBM20 or multi-domain complexes not available
    • How RRM cooperates with ZnF2 structurally unknown
  10. 2021 High

    Whether cytoplasmic mutant RBM20 acquires new RNA targets beyond its normal nuclear substrates was unknown; eCLIP showed R636S mutant gains binding to 3ʹ UTR sequences shared with ALS-associated RBPs (FUS, DDX6), and localizes to P-bodies and stress granules, revealing a splicing-independent gain-of-function pathomechanism.

    Evidence eCLIP, deep RNA-seq, super-resolution microscopy in isogenic iPSC-derived engineered heart tissues

    PMID:34732726

    Open questions at the time
    • Whether gained 3ʹ UTR binding directly causes translational dysregulation not demonstrated
    • Overlap with ALS RBP biology remains correlative
  11. 2022 High

    The nuclear import receptor for RBM20 and the phospho-regulatory logic of its RS domain were identified: TNPO3 directly imports RBM20 via its RS domain, and pathogenic RSRSP mutations disrupt this interaction; phosphorylation at 16 RS-domain sites by SRPK1/CLK1/AKT2 modulates transport, and domain-deletion models definitively separated NLS function (RS domain) from splicing function (RRM).

    Evidence Genome-wide CRISPR screen, Co-IP, direct binding assays, rescue experiments, mass spectrometry, kinase assays, RS-deletion and RRM-deletion mouse models

    PMID:35394688 PMID:35427468 PMID:36140694 PMID:37219949 PMID:37463913

    Open questions at the time
    • Precise phosphorylation code governing TNPO3 affinity not resolved
    • Whether other importins contribute in vivo not excluded
  12. 2022 Medium

    Upstream transcriptional regulation of RBM20 was largely unknown; the circadian clock factor BMAL1 was shown to regulate Rbm20 transcription in skeletal muscle, and angiotensin II signaling through MAPK/ELK1 was identified as activating the RBM20 promoter in cardiomyocytes.

    Evidence Skeletal muscle Bmal1 KO mice, dual-luciferase promoter assays, primary cardiomyocyte cultures

    PMID:31614708 PMID:36047761

    Open questions at the time
    • Relative contributions of different transcription factors to cardiac RBM20 levels not quantified
    • Chromatin-level regulation of the RBM20 locus not mapped
  13. 2025 High

    Whether reducing mutant RBM20 protein (and its granules) is therapeutic independently of restoring splicing was untested; ASO-mediated knockdown of RBM20-S639G reduced cytoplasmic granules and alleviated DCM without correcting TTN/CAMK2D/RYR2 mis-splicing, proving granule toxicity as a critical independent disease driver; separately, atrial-specific mutant expression caused AF through connexin-43 mislocalization and Ca²⁺ dysfunction independent of splicing.

    Evidence ASO treatment in S639G KI mice (prophylactic and therapeutic); atrial-specific S637A mouse model with optical mapping and Ca²⁺ imaging

    PMID:40242865 PMID:40480405

    Open questions at the time
    • Long-term safety and durability of ASO approach not established
    • Molecular link between RNP granules and connexin-43 mislocalization not defined
  14. 2025 Medium

    RARβ was identified as a direct transcriptional activator of RBM20 that binds its promoter; impaired RARβ signaling in hypertrophic hearts downregulates RBM20, and pharmacological RARβ activation with adapalene restores RBM20 expression and normalizes CACNA1C splicing.

    Evidence ChIP, dual-luciferase assay, TAC and isoproterenol mouse models, adapalene treatment

    PMID:41274546

    Open questions at the time
    • Whether RARβ activation is sufficient to normalize full RBM20 splicing program not tested
    • Therapeutic window for adapalene in DCM not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full molecular composition and toxicity mechanism of cytoplasmic RBM20 RNP granules, the structural basis of full-length RBM20 function in complex with the spliceosome, whether the TTN-nucleated trans-interacting chromatin domain is functionally required for efficient co-regulation of dispersed targets, and the precise phosphorylation code governing TNPO3-mediated nuclear import.
  • No structure of full-length RBM20 or RBM20-spliceosome complex
  • Causal requirement of TID for splicing efficiency not tested by direct perturbation
  • Complete inventory of RNP granule components and their individual contributions to toxicity unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 5 GO:0003723 RNA binding 4 GO:0140110 transcription regulator activity 3
Localization
GO:0005634 nucleus 7 GO:0005829 cytosol 6 GO:0005654 nucleoplasm 2
Pathway
R-HSA-8953854 Metabolism of RNA 6 R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 3
Partners
CACNA1CCAMK2DPTBP1RBM24TNPO3TTN

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 Loss-of-function mutation in RBM20 causes pathological titin isoform expression through disrupted alternative splicing; RBM20 regulates splicing of titin (TTN) and ~30 other conserved cardiac genes enriched for cardiomyopathy, ion homeostasis, and sarcomere biology. Positional cloning in rat model, deep sequencing of cardiac transcriptome (RNA-seq), loss-of-function rat model Nature medicine High 22466703
2014 RBM20 acts as a splicing repressor that binds predominantly within intronic sequences near 3' and 5' splice sites via a distinct UCUU RNA-recognition element; RBM20 interacts with U1 and U2 snRNPs and causes spliceosome stalling at complex A to repress exon splicing. CLIP-seq (transcriptome-wide crosslinking immunoprecipitation), RNA-seq, quantitative proteomics in cell culture and rat/human hearts The Journal of clinical investigation High 24960161
2013 RBM20 mediates titin exon skipping by binding to titin pre-mRNA to repress splicing of specific regions; nuclear speckles containing RBM20 are aggregates of RBM20 protein on partially processed titin pre-mRNAs; RBM20 uses cooperative repression and alternative 3' splice site selection to skip different subsets of titin exons. RNA binding assays, splice reporter assays, immunofluorescence, Rbm20-deficient rat model Nucleic acids research High 23307558
2016 RBM20 is required for the production of a specific subset of circular RNAs (circRNAs) originating from the I-band region of the titin gene; by excluding specific exons from titin pre-mRNA, RBM20 provides the substrate for circRNA biogenesis from this locus. circRNA profiling of ribosomal-depleted RNA, RBM20-null mice, human mutation carrier cardiac samples Circulation research High 27531932
2018 Loss of RBM20 causes aberrant splicing of CaMKIIδ (CAMK2D), shifting expression toward the δ-A isoform that activates the L-type Ca2+ current (ICa,L), leading to intracellular Ca2+ overload, increased sarcoplasmic reticulum Ca2+ content, and spontaneous SR Ca2+ releases in cardiomyocytes. Rbm20 knockout mice, cellular electrophysiology (patch clamp), intracellular Ca2+ measurements, RNA-seq Circulation High 29650543
2018 The RSRSP stretch of RBM20 functions as a critical part of its nuclear localization signal; the two serine residues in this stretch are constitutively phosphorylated, and mutations in the stretch disrupt nuclear localization of RBM20. Phospho-antibody analysis, Rbm20 S637A knock-in mouse model, cell transfection and immunofluorescence Scientific reports High 29895960
2018 The combination of RBM20's RNA recognition motif (RRM) and C-terminus is necessary and sufficient for splicing activity; ZnF2 domain contributes to splicing repression; RBM20 binds via its RRM to clusters containing UCUU motifs near titin exons and represses flanking introns; PTB4 acts as a novel titin splice regulator that counteracts RBM20 repressor activity. Splice reporter assays in tissue culture, in vitro binding assays, domain deletion constructs Nucleic acids research High 29518215
2019 TTN pre-mRNA nucleates RBM20 foci in the nucleus that drive spatial proximity between the TTN locus and other inter-chromosomal RBM20 targets (CACNA1C, CAMK2D), forming a cardiac-specific trans-interacting chromatin domain (TID) that acts as a splicing factory to promote RBM20-dependent alternative splicing. Hi-C, RNA-seq, ATAC-seq, genome editing (CRISPR) in human pluripotent stem cell-derived cardiomyocytes Nature communications High 30948719
2020 DCM-associated missense mutations in the RS domain of RBM20 (R636S) cause RBM20 mislocalization from the nucleus to the sarcoplasm where it forms dysregulated ribonucleoprotein (RNP) granules with liquid-like material properties that dock along cytoskeletal elements and fuse with stress granules. Gene-edited pig model (R636S knock-in), patient iPSC-derived cardiomyocytes, imaging of RNP granules, liquid-liquid phase separation characterization Nature medicine High 33188278
2020 Mutations in the RSRSP stretch of RBM20 (S637A knock-in) prevent localization to nuclear speckles and cause accumulation in cytoplasmic perinuclear granule-like structures; mice harboring this mutation develop severe cardiac dysfunction and spontaneous AF/ventricular arrhythmias; frame-shift deletion causing loss of RBM20 produces less severe phenotype despite identical splicing loss. Rbm20 S637A knock-in mice vs. frameshift deletion mice; echocardiography, electrocardiography, immunofluorescence Scientific reports High 33110103
2020 Structural basis of RBM20 RNA recognition: the RRM domain of RBM20 uses a coupled folding-binding mechanism via a C-terminal helix (encoded by exon 8) to specifically recognize the UCUU RNA motif; removing this helix reduces both affinity and specificity for UCUU. Crystal structure of mouse RBM20 RRM domain bound to UCUU-containing RNA, biochemical binding assays, mutagenesis Nucleic acids research High 32187365
2021 DCM-associated RBM20 missense mutations (e.g., R636S) have a gain-of-function binding preference for 3' UTR sequences shared with ALS-associated and processing-body RBPs (FUS, DDX6); mutant RBM20 localizes to cytoplasmic processing bodies (DDX6+) under basal conditions and to stress granules (G3BP1+) under acute stress, revealing splicing-independent pathogenic mechanisms. eCLIP, deep RNA-seq, super-resolution microscopy, isogenic iPSC-derived engineered heart tissues Nature communications High 34732726
2022 Pathogenic RBM20 RS-domain variants cause nuclear mislocalization because they disrupt direct interaction with Transportin-3 (TNPO3), the main nuclear importer of RBM20; mislocalized RBM20 retains splice regulatory activity but forms cytoplasmic granules; re-targeting mutant RBM20 to the nucleus via TNPO3 restores alternative splicing and dissolves granules. Genome-wide CRISPR knockout screen with image-enabled cell sorting, Co-IP, direct binding assays, rescue experiments in cell culture and animal models Nature communications High 37463913
2022 Phosphorylation of the RS domain of RBM20 at 16 sites (including S638 and S640 in the RSRSP stretch) regulates its nucleocytoplasmic transport and association with cytoplasmic ribonucleoprotein granules; phosphomimetic mutations indicate phosphorylation alone is not the direct cause of mislocalization in vitro. Middle-down mass spectrometry, Rbm20 S637A knock-in mice, quantitative RNA-interactome capture (qRIC), phosphoproteomics FASEB journal / Molecular cell High 35394688 35427468
2022 SR protein kinases SRPK1, CLK1, and AKT2 phosphorylate the S638 and S640 residues in the RSRSP stretch of RBM20 and regulate RBM20-dependent splicing of target cardiac genes. In vitro kinase assays, cell transfection, in vivo experiments with kinase inhibitors Genes Medium 36140694
2022 The RS domain of RBM20 contains the core nuclear localization signal (NLS); deletion of the RS domain (Rbm20ΔRS) causes cytoplasmic mislocalization and RBM20 granule formation along with DCM, while deletion of the RRM domain causes equivalent mis-splicing but no granule formation and no DCM; only DCM-associated RS domain mutations promote nucleocytoplasmic transport and granule assembly in vitro. RS domain deletion mouse model (Rbm20ΔRS), RRM deletion mice, NLS mapping by deletion analysis, immunocytochemistry, echocardiography JCI insight High 37219949
2022 RBM20 S639G mutation promotes RBM20 trafficking to the sarcoplasm and RNP granule formation, causing severe DCM and premature death; knock-in mice develop enlarged atria and severely impaired contractility; reduction of diastolic stiffness and impaired contractility were observed at both organ and cardiomyocyte levels. RBM20 S639G knock-in mice, echocardiography, cardiac catheterization, RNA-seq, fluorescent immunohistochemistry Journal of molecular and cellular cardiology High 35041844
2022 Adenine base editing (ABE) correction of pathogenic RBM20 R634Q and R636S mutations in iPSC-derived cardiomyocytes restores nuclear localization of RBM20, normalizes alternative splicing of cardiac genes, and eliminates RNP granule formation; systemic AAV9 delivery of ABE in Rbm20 R636Q knock-in mice restores cardiac function. Adenine base editing and prime editing in iPSCs, AAV9 systemic delivery in mice, echocardiography, RNA-seq Science translational medicine High 36417486
2013 The sequences necessary for RBM20 nuclear retention overlap the RNA binding motif and serine-arginine domain; this nuclear localization determinant is conserved across species but unique to RBM20 orthologs. Cloning of human and mouse RBM20 cDNA, expressing vectors for truncated proteins, subcellular distribution analysis in transfected cells FEBS letters Medium 23886709
2016 RBM20 and RBM24 cooperatively promote the expression of short ENH splice variants by binding the 5' intronic region of exon 11 of the enh gene; both RBM20 and RBM24 expression are repressed by hypertrophic stimulation. Co-transfection experiments, RNA immunoprecipitation, functional splicing assays FEBS letters Medium 27289039
2017 Insulin activates the PI3K-Akt-mTOR kinase axis to increase N2B titin isoform expression through RBM20 in an RBM20-dependent manner; knockdown of p70S6K1 reduces both RBM20 and N2B levels while 4E-BP1 knockdown elevates them; RBM20 levels are also regulated by insulin-induced kinase signaling. Neonatal rat cardiomyocyte cultures, kinase inhibitors, siRNA knockdown, diabetic rat model, RT-PCR for titin isoforms Biochimica et biophysica acta. Molecular basis of disease Medium 28676430
2018 RBM20 and PTBP1 cooperatively regulate alternative splicing of FHOD3, promoting exclusion of selected exons; their combined expression shifts FHOD3 isoform balance from inclusion to exclusion. Splicing reporter assays, co-transfection experiments in cell lines The international journal of biochemistry & cell biology Medium 30468920
2019 RBM20 overexpression in neonatal rat cardiomyocytes promotes inclusion of CACNA1C exon 9*, reduces L-type Ca2+ currents, and decreases CaV1.2 surface membrane expression; RBM20 binds introns flanking exon 9* by RNA immunoprecipitation. RBM20 overexpression and siRNA knockdown in neonatal rat cardiomyocytes, electrophysiology (L-type Ca2+ currents), RNA immunoprecipitation, surface expression assay International journal of molecular sciences Medium 31717392
2019 Angiotensin II activates the MAPK/ELK1 signaling pathway, which promotes transcription of RBM20 by enabling ELK1 binding to the RBM20 promoter, thereby upregulating RBM20-dependent pre-mRNA splicing of cardiac targets (titin, LDB3, CAMK2G, TRDN). Dual-luciferase promoter assay, western blotting for MAPK signaling, primary cardiomyocyte cultures with hormone treatments International journal of molecular sciences Medium 31614708
2025 Reducing pathogenic RBM20 (S639G) expression using antisense oligonucleotides (ASOs) decreases cytoplasmic RNP granules and alleviates DCM independently of restoring mis-splicing of target genes including TTN, CAMK2D, RYR2, and ANK3, demonstrating that RNP granules are a critical driver of RBM20 cardiomyopathy. ASO treatment in Rbm20 S639G knock-in mice (prophylactic and therapeutic), echocardiography, immunohistochemistry for RNP granules, RT-PCR for splicing, electrocardiography Circulation research High 40242865
2025 Cytoplasmic mutant RBM20 (S637A) expressed specifically in atria causes spontaneous atrial tachycardia and increased AF inducibility independent of splicing defects, associated with reduced connexin 43 expression/mislocalization and abnormal Ca2+ handling with altered phosphorylation of Ca2+-handling proteins. Atrial-specific mutant RBM20-expressing mouse model (SlnCre/+; LSL-Rbm20S637A), optical mapping, Ca2+ imaging, immunofluorescence Journal of molecular and cellular cardiology Medium 40480405
2022 The skeletal muscle circadian clock regulates titin isoform expression through transcriptional regulation of Rbm20; inducible skeletal muscle-specific Bmal1 knockout alters titin splicing by downregulating Rbm20 expression, leading to sarcomere length heterogeneity. Inducible skeletal muscle-specific Bmal1 knockout mice, RNAseq, LC-MS, SDS-VAGE, U7 snRNA-mediated exon skipping eLife Medium 36047761
2024 O-MAP targeted to TTN introns reveals that TTN pre-mRNA nucleates a subnuclear compartment recruiting dozens of RNA-binding and chromatin-scaffolding factors (including QKI and SAFB) along with their target transcripts; loss of RBM20 remodels nearly every facet of this architecture including cis- and trans-interacting chromosomal domains. Oligonucleotide-mediated proximity-interactome mapping (O-MAP), proximity ligation, proteomics, genome-wide chromatin and RNA interaction mapping bioRxivpreprint Medium 39574693
2025 RARβ directly binds the RBM20 promoter and activates its transcription; impaired RARβ in hypertrophic hearts downregulates RBM20, leading to increased CACNA1C exon 9* inclusion, elevated intracellular Ca2+, and hypertrophic remodeling; a selective RARβ agonist (adapalene) restores RBM20 expression and normalizes CaV1.2 splicing. Chromatin immunoprecipitation, dual-luciferase promoter assay, NRVMs, TAC and isoproterenol mouse models, adapalene treatment Journal of molecular and cellular cardiology Medium 41274546

Source papers

Stage 0 corpus · 99 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing. Nature medicine 472 22466703
2016 RBM20 Regulates Circular RNA Production From the Titin Gene. Circulation research 242 27531932
2018 RBM20 Mutations Induce an Arrhythmogenic Dilated Cardiomyopathy Related to Disturbed Calcium Handling. Circulation 179 29650543
2014 RNA-binding protein RBM20 represses splicing to orchestrate cardiac pre-mRNA processing. The Journal of clinical investigation 178 24960161
2010 Identification of novel mutations in RBM20 in patients with dilated cardiomyopathy. Clinical and translational science 148 20590677
2011 Genetic variation in the alternative splicing regulator RBM20 is associated with dilated cardiomyopathy. Heart rhythm 134 22004663
2022 Precise genomic editing of pathogenic mutations in RBM20 rescues dilated cardiomyopathy. Science translational medicine 121 36417486
2019 Regional Variation in RBM20 Causes a Highly Penetrant Arrhythmogenic Cardiomyopathy. Circulation. Heart failure 119 30871351
2019 Dynamics of genome reorganization during human cardiogenesis reveal an RBM20-dependent splicing factory. Nature communications 119 30948719
2013 Rbm20 regulates titin alternative splicing as a splicing repressor. Nucleic acids research 119 23307558
2016 Experimentally Increasing the Compliance of Titin Through RNA Binding Motif-20 (RBM20) Inhibition Improves Diastolic Function In a Mouse Model of Heart Failure With Preserved Ejection Fraction. Circulation 100 27630136
2020 Dysregulated ribonucleoprotein granules promote cardiomyopathy in RBM20 gene-edited pigs. Nature medicine 91 33188278
2017 Severe DCM phenotype of patient harboring RBM20 mutation S635A can be modeled by patient-specific induced pluripotent stem cell-derived cardiomyocytes. Journal of molecular and cellular cardiology 76 28941705
2015 Modeling structural and functional deficiencies of RBM20 familial dilated cardiomyopathy using human induced pluripotent stem cells. Human molecular genetics 75 26604136
2019 Pathogenic RBM20-Variants Are Associated With a Severe Disease Expression in Male Patients With Dilated Cardiomyopathy. Circulation. Heart failure 71 30871348
2013 Whole exome sequencing identifies a causal RBM20 mutation in a large pedigree with familial dilated cardiomyopathy. Circulation. Cardiovascular genetics 57 23861363
2018 Alternative Splicing Regulator RBM20 and Cardiomyopathy. Frontiers in molecular biosciences 54 30547036
2018 Phosphorylation of the RSRSP stretch is critical for splicing regulation by RNA-Binding Motif Protein 20 (RBM20) through nuclear localization. Scientific reports 53 29895960
2020 iPSC Modeling of RBM20-Deficient DCM Identifies Upregulation of RBM20 as a Therapeutic Strategy. Cell reports 51 32905764
2020 New Insights in RBM20 Cardiomyopathy. Current heart failure reports 49 32789749
2021 Gain-of-function cardiomyopathic mutations in RBM20 rewire splicing regulation and re-distribute ribonucleoprotein granules within processing bodies. Nature communications 47 34732726
2014 Rbm20-deficient cardiogenesis reveals early disruption of RNA processing and sarcomere remodeling establishing a developmental etiology for dilated cardiomyopathy. Human molecular genetics 46 24584570
2016 Reducing RBM20 activity improves diastolic dysfunction and cardiac atrophy. Journal of molecular medicine (Berlin, Germany) 41 27889803
2020 A missense mutation in the RSRSP stretch of Rbm20 causes dilated cardiomyopathy and atrial fibrillation in mice. Scientific reports 40 33110103
2021 RBM20-Related Cardiomyopathy: Current Understanding and Future Options. Journal of clinical medicine 39 34575212
2021 Therapeutic inhibition of RBM20 improves diastolic function in a murine heart failure model and human engineered heart tissue. Science translational medicine 36 34851694
2013 Pathophysiological defects and transcriptional profiling in the RBM20-/- rat model. PloS one 36 24367651
2017 RBM20, a potential target for treatment of cardiomyopathy via titin isoform switching. Biophysical reviews 33 28577155
2020 The Emerging Role of the RBM20 and PTBP1 Ribonucleoproteins in Heart Development and Cardiovascular Diseases. Genes 32 32276354
2018 Splicing Factor RBM20 Regulates Transcriptional Network of Titin Associated and Calcium Handling Genes in The Heart. International journal of biological sciences 32 29725258
2018 Molecular basis of titin exon exclusion by RBM20 and the novel titin splice regulator PTB4. Nucleic acids research 31 29518215
2016 Pharmacological Modulation of Calcium Homeostasis in Familial Dilated Cardiomyopathy: An In Vitro Analysis From an RBM20 Patient-Derived iPSC Model. Clinical and translational science 31 27105042
2020 Cardiomyopathy-associated mutations in the RS domain affect nuclear localization of RBM20. Human mutation 29 32840935
2017 Insulin regulates titin pre-mRNA splicing through the PI3K-Akt-mTOR kinase axis in a RBM20-dependent manner. Biochimica et biophysica acta. Molecular basis of disease 29 28676430
2023 Mislocalization of pathogenic RBM20 variants in dilated cardiomyopathy is caused by loss-of-interaction with Transportin-3. Nature communications 27 37463913
2013 Identification of nuclear retention domains in the RBM20 protein. FEBS letters 27 23886709
2016 RBM20 and RBM24 cooperatively promote the expression of short enh splice variants. FEBS letters 25 27289039
2022 RBM20 phosphorylation and its role in nucleocytoplasmic transport and cardiac pathogenesis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24 35394688
2021 The Combined Human Genotype of Truncating TTN and RBM20 Mutations Is Associated with Severe and Early Onset of Dilated Cardiomyopathy. Genes 24 34201072
2018 Muscle-Specific Mis-Splicing and Heart Disease Exemplified by RBM20. Genes 23 29304022
2022 RBM20S639G mutation is a high genetic risk factor for premature death through RNA-protein condensates. Journal of molecular and cellular cardiology 21 35041844
2018 Drug discovery with an RBM20 dependent titin splice reporter identifies cardenolides as lead structures to improve cardiac filling. PloS one 20 29889873
2018 RNA-binding proteins RBM20 and PTBP1 regulate the alternative splicing of FHOD3. The international journal of biochemistry & cell biology 20 30468920
2024 Mechanisms of RBM20 Cardiomyopathy: Insights From Model Systems. Circulation. Genomic and precision medicine 18 38288598
2022 The skeletal muscle circadian clock regulates titin splicing through RBM20. eLife 18 36047761
2021 RBM20 Is a Candidate Gene for Hypertrophic Cardiomyopathy. The Canadian journal of cardiology 18 34333030
2023 Loss of Cardiac Splicing Regulator RBM20 Is Associated With Early-Onset Atrial Fibrillation. JACC. Basic to translational science 17 38510713
2020 Structural basis of UCUU RNA motif recognition by splicing factor RBM20. Nucleic acids research 17 32187365
2023 Disruption of the nuclear localization signal in RBM20 is causative in dilated cardiomyopathy. JCI insight 15 37219949
2023 Sorafenib induces cardiotoxicity through RBM20-mediated alternative splicing of sarcomeric and mitochondrial genes. Pharmacological research 15 38006979
2022 Proteome-wide quantitative RNA-interactome capture identifies phosphorylation sites with regulatory potential in RBM20. Molecular cell 15 35427468
2016 Emerging Role for RBM20 and its Splicing Substrates in Cardiac Function and Heart Failure. Current pharmaceutical design 13 27396593
2022 RBM20, a Therapeutic Target to Alleviate Myocardial Stiffness via Titin Isoforms Switching in HFpEF. Frontiers in cardiovascular medicine 12 35783855
2021 The ryanodine receptor stabilizer S107 ameliorates contractility of adult Rbm20 knockout rat cardiomyocytes. Physiological reports 12 34523260
2019 Angiotensin II Influences Pre-mRNA Splicing Regulation by Enhancing RBM20 Transcription Through Activation of the MAPK/ELK1 Signaling Pathway. International journal of molecular sciences 12 31614708
2022 I536T variant of RBM20 affects splicing of cardiac structural proteins that are causative for developing dilated cardiomyopathy. Journal of molecular medicine (Berlin, Germany) 11 36198914
2020 Generation of pluripotent stem cell lines and CRISPR/Cas9 modified isogenic controls from a patient with dilated cardiomyopathy harboring a RBM20 p.R634W mutation. Stem cell research 11 32674065
2022 Deep phenotyping of two preclinical mouse models and a cohort of RBM20 mutation carriers reveals no sex-dependent disease severity in RBM20 cardiomyopathy. American journal of physiology. Heart and circulatory physiology 10 36367695
2021 Malignant Arrhythmogenic Role Associated with RBM20: A Comprehensive Interpretation Focused on a Personalized Approach. Journal of personalized medicine 10 33671899
2020 Whole-exome sequencing reveals two de novo variants in the RBM20 gene in two Chinese patients with left ventricular non-compaction cardiomyopathy. Pediatric investigation 10 32851336
2018 Phenotypic Heterogeneity within Members of a Family Carrying the Same RBM20 Mutation R634W. Cardiology 10 30557877
2021 RBM20-Associated Ventricular Arrhythmias in a Patient with Structurally Normal Heart. Genes 9 33450993
2021 Phenotype and progression among patients with dilated cardiomyopathy and RBM20 mutations. European journal of medical genetics 9 34174465
2022 Dilated cardiomyopathy caused by a pathogenic nucleotide variant in RBM20 in an Iranian family. BMC medical genomics 8 35527250
2019 RBM20 Regulates CaV1.2 Surface Expression by Promoting Exon 9* Inclusion of CACNA1C in Neonatal Rat Cardiomyocytes. International journal of molecular sciences 8 31717392
2018 Characterization of TTN Novex Splicing Variants across Species and the Role of RBM20 in Novex-Specific Exon Splicing. Genes 8 29438341
2022 SR Protein Kinases Regulate the Splicing of Cardiomyopathy-Relevant Genes via Phosphorylation of the RSRSP Stretch in RBM20. Genes 7 36140694
2019 Whole exome sequencing in a large pedigree with DCM identifies a novel mutation in RBM20. Acta cardiologica 7 31583969
2024 Loss of endogenous estrogen alters mitochondrial metabolism and muscle clock-related protein Rbm20 in female mdx mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 6 38847487
2022 Pathogenic variant of RBM20 in a multiplex family with hypertrophic cardiomyopathy. Human genome variation 6 35181673
2022 Rbm20 ablation is associated with changes in the expression of titin-interacting and metabolic proteins. Molecular omics 6 35762193
2025 Reducing Granules Without Splicing Restoration Alleviates RBM20 Cardiomyopathy. Circulation research 5 40242865
2022 Rbm20ΔRRM Mice, Expressing a Titin Isoform with Lower Stiffness, Are Protected from Mechanical Ventilation-Induced Diaphragm Weakness. International journal of molecular sciences 5 36555335
2024 Nascent transcript O-MAP reveals the molecular architecture of a single-locus subnuclear compartment built by RBM20 and the TTN RNA. bioRxiv : the preprint server for biology 4 39574693
2021 RBM20-Mediated Pre-mRNA Splicing Has Muscle-Specificity and Differential Hormonal Responses between Muscles and in Muscle Cell Cultures. International journal of molecular sciences 3 33805770
2021 Familial dilated cardiomyopathy with RBM20 mutation in an Indian patient: a case report. The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology 3 34021826
2025 A single RBM20 missense variant is a potential contributor to dilated cardiomyopathy and/or isolated left ventricular dilatation in the Emilia Romagna region of Italy. International journal of cardiology 2 39855353
2025 Cytoplasmic mutant RBM20 causes arrhythmogenicity in murine atria. Journal of molecular and cellular cardiology 2 40480405
2024 Integrated proteomics and transcriptomics analysis reveals insights into differences in premature mortality associated with disparate pathogenic RBM20 variants. Journal of molecular and cellular cardiology 2 39490642
2023 Generation of an RBM20-mutation-associated left-ventricular non-compaction cardiomyopathy iPSC line (UMGi255-A) into a DCM genetic background to investigate monogenetic cardiomyopathies. Stem cell research 2 38141360
2021 RBM20 mutation and ventricular arrhythmias in a young patient with dilated cardiomyopathy: a case report. American journal of cardiovascular disease 2 34322310
2025 Co-existence of RBM20 and KCNQ1 gene mutations in a patient with long QT syndrome and dilated cardiomyopathy. "Which came first: Chicken or the egg?". Indian pacing and electrophysiology journal 1 40158693
2025 The contribution of RBM20 truncating variants to human cardiomyopathy. medRxiv : the preprint server for health sciences 1 40778137
2025 Prime editing corrects the dilated cardiomyopathy causing RBM20-P633L-mutation in human cardiomyocytes. Molecular therapy. Nucleic acids 1 41210585
2024 Deletion of RBM20 exon 9 impairs skeletal muscle growth and satellite cell function in pigs. Biochemical and biophysical research communications 1 39632296
2026 Early Onset Heart Failure due to RBM20 Variant: A Case Report Emphasizing Genetic Diagnosis and Arrhythmic Risk Stratification. Clinical case reports 0 41567528
2026 Generation of two induced pluripotent stem cell lines from dilated cardiomyopathy patients carrying RBM20 mutations. Stem cell research 0 41570362
2026 Molecular biological effect of Rbm20 I538T knock-in mice on skeletal muscle. Legal medicine (Tokyo, Japan) 0 41795487
2026 RBM20 Truncating Variants and Human Cardiomyopathy. JAMA cardiology 0 41949880
2025 Age at onset and clinical course of RBM20-mediated cardiomyopathy. Scientific reports 0 40155426
2025 Profiling of RBM20-Regulated CaMKIIδ Splice Variants Across the Heart, Skeletal Muscle, and Olfactory Bulbs. Genes to cells : devoted to molecular & cellular mechanisms 0 40343393
2025 Transcriptomic analysis implicates the involvement of RBM20 in Fuchs' endothelial corneal dystrophy with TCF4 repeat expansion. PloS one 0 40961119
2025 Q373fs variant of RBM20 affects splicing and expression of cardiac-related genes and cardiac function: human sudden death case and mouse experiments. Human molecular genetics 0 41076636
2025 Rbm20 antisense oligonucleotides alleviate diastolic dysfunction in a mouse model of cardiometabolic heart failure (HFpEF). Cardiovascular research 0 41104480
2025 RNA binding protein RBM20 regulates turtle temperature-dependent sex determination by repressing the splicing of Wt1 KTS. Science advances 0 41237229
2025 Impaired retinoic acid signaling mediated Rbm20 downregulation induces aberrant splicing of CaV1.2 calcium channel: implications in myocardial hypertrophy. Journal of molecular and cellular cardiology 0 41274546
2023 [Research progress on the expression of the RBM20 gene in dilated cardiomyopathy]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 0 37905768
2022 A quantitative RT-PCR protocol to adapt and quantify RBM20-dependent exon splicing of targets at the human locus. STAR protocols 0 35106501
2019 Megaesophagus Is a Major Pathological Condition in Rats With a Large Deletion in the Rbm20 Gene. Veterinary pathology 0 31221019