Z‐band and M‐band titin splicing and regulation by RNA binding motif 20 in striated muscles
Year: 2018
Type: article
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.
Source: Journal of Cellular Biochemistry
DOI: 10.1002/jcb.27328
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: American Heart Association, University of Wyoming, Institut National de la Santé et de la Recherche Médicale, China Scholarship Council, National Institutes of Health, National Institute of Food and Agriculture, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1065043603, The role of posttranslational modification of RBM20 in regulating titin isoform transition, G1542379004, G3514457801, Cortisol regulation of perinatal adipose tissue and sheep neonatal leptin peak, G4379707475, G5817462511, Deciphering Myofilament Modifications in Ischemic Cardiomyopathy, Wyoming IDeA Networks for Biomedical Research Excellence Phase 4, Top-Down Proteomics of Myofilaments in Heart Failure
OpenAlex ID: W2888543983