TY - JOUR TI - QKI is a critical pre-mRNA alternative splicing regulator of cardiac myofibrillogenesis and contractile function AU - Chen, Xinyun AU - Liu, Ying AU - Xu, Chen AU - Ba, Lina AU - Liu, Zhuo AU - Li, Xiuya AU - Huang, Jie AU - Simpson, Ed AU - Gao, Hongyu AU - Cao, Dayan AU - Sheng, Wei AU - Qi, Hanping AU - Ji, Hongrui AU - Sanderson, Maria AU - Cai, Chen-Leng AU - Li, Xiaohui AU - Yang, Lei AU - Na, Jie AU - Yamamura, Kenichi AU - Liu, Yunlong AU - Huang, Guoying AU - Shou, Weinian AU - Sun, Ning T2 - Nature Communications AB - The RNA-binding protein QKI belongs to the hnRNP K-homology domain protein family, a well-known regulator of pre-mRNA alternative splicing and is associated with several neurodevelopmental disorders. Qki is found highly expressed in developing and adult hearts. By employing the human embryonic stem cell (hESC) to cardiomyocyte differentiation system and generating QKI-deficient hESCs (hESCs-QKIdel) using CRISPR/Cas9 gene editing technology, we analyze the physiological role of QKI in cardiomyocyte differentiation, maturation, and contractile function. hESCs-QKIdel largely maintain normal pluripotency and normal differentiation potential for the generation of early cardiogenic progenitors, but they fail to transition into functional cardiomyocytes. In this work, by using a series of transcriptomic, cell and biochemical analyses, and the Qki-deficient mouse model, we demonstrate that QKI is indispensable to cardiac sarcomerogenesis and cardiac function through its regulation of alternative splicing in genes involved in Z-disc formation and contractile physiology, suggesting that QKI is associated with the pathogenesis of certain forms of cardiomyopathies. DA - 2021/01/04/ PY - 2021 DO - 10.1038/s41467-020-20327-5 DP - www.nature.com VL - 12 IS - 1 SP - 89 LA - en SN - 2041-1723 UR - https://www.nature.com/articles/s41467-020-20327-5 Y2 - 2021/01/04/18:56:48 ER -