Back to Search Start Over

QKI is a critical pre-mRNA alternative splicing regulator of cardiac myofibrillogenesis and contractile function

Authors :
Jie Na
Xiaohui Li
Xinyun Chen
Zhuo Liu
Jie Huang
Guoying Huang
Da-yan Cao
Ning Sun
Lei Yang
Hongyu Gao
Wei Sheng
Xiuya Li
Weinian Shou
Edward Simpson
Ken Ichi Yamamura
Ying Liu
Hanping Qi
Hongrui Ji
Chen Xu
Yunlong Liu
Chen-Leng Cai
Maria Sanderson
Lina Ba
Source :
Nature Communications, Vol 12, Iss 1, Pp 1-18 (2021), Nature Communications
Publication Year :
2021
Publisher :
Nature Portfolio, 2021.

Abstract

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.<br />RNA binding protein Quaking (QKI) is known for its broad function in pre-mRNA splicing and modification and its association with several neurodevelopmental disorders. Here the authors reveal that QKI-mediated regulation of RNA splicing is indispensable to cardiac development and contractile physiology.

Details

Language :
English
ISSN :
20411723
Volume :
12
Issue :
1
Database :
OpenAIRE
Journal :
Nature Communications
Accession number :
edsair.doi.dedup.....a63cab455a7047761000d3d438a9a08f