Browsing by Author "Chen, Xinyun"

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    The Emerging Roles of the RNA Binding Protein QKI in Cardiovascular Development and Function
    (Frontiers Media, 2021-06-16) Chen, Xinyun; Yin, Jianwen; Cao, Dayan; Xiao, Deyong; Zhou, Zhongjun; Liu, Ying; Shou, Weinian; Pediatrics, School of Medicine
    RNA binding proteins (RBPs) have a broad biological and physiological function and are critical in regulating pre-mRNA posttranscriptional processing, intracellular migration, and mRNA stability. QKI, also known as Quaking, is a member of the signal transduction and activation of RNA (STAR) family, which also belongs to the heterogeneous nuclear ribonucleoprotein K- (hnRNP K-) homology domain protein family. There are three major alternatively spliced isoforms, QKI-5, QKI-6, and QKI-7, differing in carboxy-terminal domains. They share a common RNA binding property, but each isoform can regulate pre-mRNA splicing, transportation or stability differently in a unique cell type-specific manner. Previously, QKI has been known for its important role in contributing to neurological disorders. A series of recent work has further demonstrated that QKI has important roles in much broader biological systems, such as cardiovascular development, monocyte to macrophage differentiation, bone metabolism, and cancer progression. In this mini-review, we will focus on discussing the emerging roles of QKI in regulating cardiac and vascular development and function and its potential link to cardiovascular pathophysiology.
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    QKI is a critical pre-mRNA alternative splicing regulator of cardiac myofibrillogenesis and contractile function
    (Springer Nature, 2021-01-04) Chen, Xinyun; Liu, Ying; Xu, Chen; Ba, Lina; Liu, Zhuo; Li, Xiuya; Huang, Jie; Simpson, Ed; Gao, Hongyu; Cao, Dayan; Sheng, Wei; Qi, Hanping; Ji, Hongrui; Sanderson, Maria; Cai, Chen-Leng; Li, Xiaohui; Yang, Lei; Na, Jie; Yamamura, Kenichi; Liu, Yunlong; Huang, Guoying; Shou, Weinian; Sun, Ning; Pediatrics, School of Medicine
    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.