RBM20, a potential target for treatment of cardiomyopathy via titin isoform switching

2018-04-09T14:27:45Z (GMT) by Wei Guo Mingming Sun
<p>Cardiomyopathy, also known as heart muscle disease,</p> <p>is an unfavorable condition leading to alterations in myocardial</p> <p>contraction and/or impaired ability of ventricular filling.</p> <p>The onset and development of cardiomyopathy have not</p> <p>currently been well defined. Titin is a giant multifunctional</p> <p>sarcomeric filament protein that provides passive stiffness to</p> <p>cardiomyocytes and has been implicated to play an important</p> <p>role in the origin and development of cardiomyopathy and</p> <p>heart failure. Titin-based passive stiffness can be mainly adjusted</p> <p>by isoform switching and post-translational modifications</p> <p>in the spring regions. Recently, genetic mutations of TTN</p> <p>have been identified that can also contribute to variable passive</p> <p>stiffness, though the detailed mechanisms remain unclear.</p> <p>In this review, we will discuss titin isoform switching as it</p> <p>relates to alternative splicing during development stages and</p> <p>differences between species and muscle types.We provide an</p> <p>update on the regulatory mechanisms of TTN splicing controlled</p> <p>by RBM20 and cover the roles of TTN splicing in</p> <p>adjusting the diastolic stiffness and systolic compliance of</p> <p>the healthy and the failing heart. Finally, this review attempts</p> <p>to provide future directions for RBM20 as a potential target</p> <p>for pharmacological intervention in cardiomyopathy and heart</p> <p>failure.</p>