ArticleNucleic acids research2018
Molecular basis of titin exon exclusion by RBM20 and the novel titin splice regulator PTB4.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Novel Truncating Variant c.1222DupC inCirculation. Genomic and precision medicine · 2026Article
- Regulation of Tau Alternative Splicing: A Novel Role for the Ribonucleoprotein RBM20.International journal of molecular sciences · 2026Article
- Myocardial Recovery With Mechanical Circulatory Support Is Linked to Alternative Splicing and Subcellular Localization of CAMK2D.Circulation · 2026Article
- Dilated cardiomyopathy-associated RNA-binding motif protein 20 regulates long pre-mRNAs in neurons.eLife · 2026Article
- Cytoplasmic CaMKIIδ-B prevents myocardial recovery in heart failure.bioRxiv : the preprint server for biology · 2025Article
- Antisense-mediated regulation of exon usage in the elastic spring region of Titin modulates sarcomere function.Cardiovascular research · 2025Article
- Molecular Regulation of Cardiomyocyte Maturation.Current cardiology reports · 2025Review
- Nascent transcript O-MAP reveals the molecular architecture of a single-locus subnuclear compartment built by RBM20 and thebioRxiv : the preprint server for biology · 2024Article
- Loss of Cardiac Splicing RegulatorJACC. Basic to translational science · 2024Article
- Mechanisms of RBM20 Cardiomyopathy: Insights From Model Systems.Circulation. Genomic and precision medicine · 2024Review
- Titin: roles in cardiac function and diseases.Frontiers in physiology · 2024Review
- [Research progress on the expression of theZhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2023Review
- Rationally designed stapled peptides allosterically inhibit PTBP1-RNA-binding.Chemical science · 2023Article
- Cardiac splicing as a diagnostic and therapeutic target.Nature reviews. Cardiology · 2023Review
- Mislocalization of pathogenic RBM20 variants in dilated cardiomyopathy is caused by loss-of-interaction with Transportin-3.Nature communications · 2023Article
- Disruption of the nuclear localization signal in RBM20 is causative in dilated cardiomyopathy.JCI insight · 2023Article
- CHERP Regulates the Alternative Splicing of pre-mRNAs in the Nucleus.International journal of molecular sciences · 2022Article
- SLM2 Is A Novel Cardiac Splicing Factor Involved in Heart Failure due to Dilated Cardiomyopathy.Genomics, proteomics & bioinformatics · 2022Article
- RBM20, a Therapeutic Target to Alleviate Myocardial StiffnessFrontiers in cardiovascular medicine · 2022Review
- RBM20-Related Cardiomyopathy: Current Understanding and Future Options.Journal of clinical medicine · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA-binding motif protein 20 (RBM20) is a cardiac splice regulator that adapts cardiac filling via its diverse substrates-including the sarcomeric protein titin. The molecular basis and regulation of RBM20-dependent exon exclusion are largely unknown. In tissue culture experiments, we show that the combination of RNA recognition motif (RRM) and C-terminus is necessary and sufficient for RBM20 activity, indicating an important function of the ZnF2 domain in splicing repression. Using splice reporter and in vitro binding assays targeting titin exons 241-243, we identified a minimal genomic segment that is necessary for RBM20-mediated splicing repression of the alternative exon. Here, RBM20 binds the cluster containing most RBM20 binding motifs through its RRM domain and represses the upstream and downstream introns. For subsequent exon exclusion, specific regions upstream, downstream and within the alternative exon 242 are required. Regulation of exon exclusion involves PTB4 as a novel titin splice regulator, which counteracts RBM20 repressor activity in HEK293 cells. Together, these mechanistic insights into the regulation and action of RBM20 and PTB4 provide a basis for the future development of RBM20 modulators that adapt titin elasticity in cardiac disease.
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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.