ArticleJournal of cellular biochemistry2018
Z-band and M-band titin splicing and regulation by RNA binding motif 20 in striated muscles.
Article in Journal of cellular biochemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Novel Mutations in Titin Exon 363 With Different Phenotypes Including a Founder Mutation in Eastern Europe.European journal of neurology · 2025Article
- Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy.Nature genetics · 2024Article
- The RNA-binding protein QKI governs a muscle-specific alternative splicing program that shapes the contractile function of cardiomyocytes.Cardiovascular research · 2023Article
- Contributions of Titin and Collagen to Passive Stress in Muscles fromInternational journal of molecular sciences · 2022Article
- RBM20-Mediated Pre-mRNA Splicing Has Muscle-Specificity and Differential Hormonal Responses between Muscles and in Muscle Cell Cultures.International journal of molecular sciences · 2021Article
- Angiotensin II Influences Pre-mRNA Splicing Regulation by EnhancingInternational journal of molecular sciences · 2019Article
- Dysregulation of Circular RNAs in Myotonic Dystrophy Type 1.International journal of molecular sciences · 2019Article
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Authors and funding
10 authors.
Funding
Abstract
Titin (TTN) has multifunctional roles in sarcomere assembly, mechanosignaling transduction, and muscle stiffness. TTN splicing generates variable protein sizes with different functions. Therefore, understanding TTN splicing is important to develop a novel treatment for TTN-based diseases. The I-band TTN splicing regulated by RNA binding motif 20 (RBM20) has been extensively studied. However, the Z- and M-band splicing and regulation remain poorly understood. Herein, we aimed to define the Z- and M-band splicing in striated muscles and determined whether RBM20 regulates the Z- and M-band splicing. We discovered four new Z-band TTN splicing variants, and one of them dominates in mouse, rat, sheep, and human hearts. But only one form can be detected in frog and chicken hearts. In skeletal muscles, three new Z repeats (Zr) were detected, and Zr4 to 6 exclusion dominates in the fast muscles, whereas Zr4 skipping dominates in the slow muscle. No developmental changes were detected in the Z-band. In the M-band, two new variants were discovered with alternative 3' splice site in exon363 (Mex5) and alternative 5' splice site in intron 362. However, only the sheep heart expresses two new variants rather than other species. Skeletal muscles express three M-band variants with altered ratios of Mex5 inclusion to Mex5 exclusion. Finally, we revealed that RBM20 does not regulate the Z- and M-band splicing in the heart, but does in skeletal muscles. Taken together, we characterized the Z- and M-band splicing and provided the first evidence of the role of RBM20 in the Z- and M-band TTN splicing.
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