Global RNA editing identification and characterization during human pluripotent-to-cardiomyocyte differentiation

Molecular Therapy: Nucleic Acids

Hui-fang Liu¹  Li-bo Qiao²  Juan Chen³  Lu Wang³  Yan Lin³  Fang-bin Wang³  Jian Liu³ 

[1] Corresponding author: Juan Chen, School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui 230009, China.;Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, China;School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui 230009, China;

关键词: cardiomyocyte differentiation;    RNA editing;    ADAR;    functional consequence;    heart disease;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: RNA editing is widely involved in stem cell differentiation and development; however, RNA editing events during human cardiomyocyte differentiation have not yet been characterized and elucidated. Here, we identified genome-wide RNA editing sites and systemically characterized their genomic distribution during four stages of human cardiomyocyte differentiation. It was found that the expression level of ADAR1 affected the global number of adenosine to inosine (A-to-I) editing sites but not the editing degree. Next, we identified 43, 163, 544, and 141 RNA editing sites that contribute to changes in amino acid sequences, variation in alternative splicing, alterations in miRNA-target binding, and changes in gene expression, respectively. Generally, RNA editing showed a stage-specific pattern with 211 stage-shared editing sites. Interestingly, cardiac muscle contraction and heart-disease-related pathways were enriched by cardio-specific editing genes, emphasizing the connection between cardiomyocyte differentiation and heart diseases from the perspective of RNA editing. Finally, it was found that these RNA editing sites are also related to several congenital and noncongenital heart diseases. Together, our study provides a new perspective on cardiomyocyte differentiation and offers more opportunities to understand the mechanisms underlying cell fate determination, which can promote the development of cardiac regenerative medicine and therapies for human heart diseases.

【 授权许可】

Unknown