The RNA-binding protein QKI governs a muscle-specific alternative splicing program that shapes the contractile function of cardiomyocytes.

Alternative splicing generates protein isoforms to maintain mechanical, structural, and metabolic properties of cardiomyocytes. We are the first to show that QKI is one of the essential splicing factors in the adult heart. During heart failure, alternative splicing of numerous genes is altered, thereby affecting cardiac function. Recent observations that QKI expression is downregulated in hearts of heart failure patients indicates that loss of QKI-mediated processes contributes to decreased sarcomere organization in these patients. Modulation of QKI activity may serve as a future therapeutic strategy to adapt cardiac isoform expression and improve cardiac function in heart failure patients.