RBM20, a Potential Target for Treatment of Cardiomyopathy Via Titin Isoform Switching

Overview

Journal Biophys Rev

Publisher Springer

Specialty Biophysics

Date 2017 Jun 4

PMID 28577155

Citations 23

Authors

Wei Guo

Mingming Sun

Affiliations

Soon will be listed here.

Abstract

Cardiomyopathy, also known as heart muscle disease, is an unfavorable condition leading to alterations in myocardial contraction and/or impaired ability of ventricular filling. The onset and development of cardiomyopathy have not currently been well defined. Titin is a giant multifunctional sarcomeric filament protein that provides passive stiffness to cardiomyocytes and has been implicated to play an important role in the origin and development of cardiomyopathy and heart failure. Titin-based passive stiffness can be mainly adjusted by isoform switching and post-translational modifications in the spring regions. Recently, genetic mutations of TTN have been identified that can also contribute to variable passive stiffness, though the detailed mechanisms remain unclear. In this review, we will discuss titin isoform switching as it relates to alternative splicing during development stages and differences between species and muscle types. We provide an update on the regulatory mechanisms of TTN splicing controlled by RBM20 and cover the roles of TTN splicing in adjusting the diastolic stiffness and systolic compliance of the healthy and the failing heart. Finally, this review attempts to provide future directions for RBM20 as a potential target for pharmacological intervention in cardiomyopathy and heart failure.

Citing Articles

Titin: roles in cardiac function and diseases.

Stroik D, Gregorich Z, Raza F, Ge Y, Guo W Front Physiol. 2024; 15:1385821.

PMID: 38660537 PMC: 11040099. DOI: 10.3389/fphys.2024.1385821.

Mechanisms of RBM20 Cardiomyopathy: Insights From Model Systems.

Gregorich Z, Zhang Y, Kamp T, Granzier H, Guo W Circ Genom Precis Med. 2024; 17(1):e004355.

PMID: 38288598 PMC: 10923161. DOI: 10.1161/CIRCGEN.123.004355.

Signaling network model of cardiomyocyte morphological changes in familial cardiomyopathy.

Khalilimeybodi A, Riaz M, Campbell S, Omens J, McCulloch A, Qyang Y J Mol Cell Cardiol. 2022; 174:1-14.

PMID: 36370475 PMC: 10230857. DOI: 10.1016/j.yjmcc.2022.10.006.

I536T variant of RBM20 affects splicing of cardiac structural proteins that are causative for developing dilated cardiomyopathy.

Yamamoto T, Sano R, Miura A, Imasaka M, Naito Y, Nishiguchi M J Mol Med (Berl). 2022; 100(12):1741-1754.

PMID: 36198914 PMC: 9691496. DOI: 10.1007/s00109-022-02262-8.

SR Protein Kinases Regulate the Splicing of Cardiomyopathy-Relevant Genes via Phosphorylation of the RSRSP Stretch in RBM20.

Sun M, Jin Y, Zhang Y, Gregorich Z, Ren J, Ge Y Genes (Basel). 2022; 13(9).

PMID: 36140694 PMC: 9498672. DOI: 10.3390/genes13091526.

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