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

Abstract

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.

Emerging role of the RNA-editing enzyme ADAR1 in stem cell fate and function

“…The expression level of ADAR1 was found to affect the global number of adenosine-to-inosine (A-to-I) editing sites but not the degree of editing. They found that these RNA editing sites are associated with several congenital and noncongenital heart diseases, thereby highlighting the link between cardiomyocyte differentiation and heart disease from an RNA editing perspective [ 96 ].…”

Unifying Different Cancer Theories in a Unique Tumour Model: Chronic Inflammation and Deaminases as Meeting Points

“…Focusing on RNA editing activity, a recent study identified several A-to-I editing events during human pluripotent stem cell-to-cardiomyocyte differentiation. Specifically, a minor (but significant) proportion of them were located within transcript coding sequences leading to amino acid changes [ 45 ], which may contribute to the generation of new proteins with distinct functions. In parallel with this, it has been reported that A-to-I editing within the mRNA 3′-untranslated region may represent a frequent event in many malignancies and can modify miRNA-binding motifs altering the miRNA putative targets.…”