Abstract 16901: A Computational Framework to Estimate the Consequences of Cardiac RNA Editing Events at Single-Cell Resolution

• Published in: Circulation (New York, N.Y.) Vol. 148; no. Suppl_1; p. A16901
• Main Authors: Srivastava, Prashant, Hassani, Mohamed, Ji, Jiahui, Guan, Yingshu, Punjabi, Prakash, Emanueli, Costanza
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 07.11.2023
• Subjects: Gene expression; Systems biology; Genomics
• DOI: 10.1161/circ.148.suppl_1.16901
• ISSN: 0009-7322

Introduction: RNA is a highly dynamic molecule subject to various epigenetic modifications. One such process is RNA editing, a tightly regulated mechanism that introduces alterations to RNA nucleotides without affecting the DNA template. RNA editing serves as a mechanism for expanding and diversifying the functional repertoire of proteins. In the context of the heart, the RNA editors assume crucial roles in preserving cardiac function. Despite the importance of RNA editing, there are no framework to evaluate consequence of synonymous RNA editing events. Synonymous RNA editing events can affect mRNA stability, translation efficiency, protein folding, and even protein-protein interactions. These subtle changes in the coding region can influence gene expression, protein synthesis, and ultimately, cellular function. Research question: What are the functional consequences of RNA editing events in different types of cardiac cells? Methods: To estimate the RNA structural metrics, we employed the Vienna RNA package software. This comprehensive package provides a range of metrics for quantifying RNA secondary structures. Results: We have developed a framework to profile RNA editing and analyse synonymous events using new and existing single-cell datasets. Our framework enables users to explore the distribution of RNA editing events across different cell types and states, as well as analyse the functional consequences of these events. Here, to demonstrate its efficacy, we have applied our framework on healthy hearts. We identified highly edited cell types such as cardiomyocytes, fibroblasts, endothelial cells, macrophages, and pericytes, with over 1,000 edited sites. Interestingly, more than 50% of these edited sites enhanced secondary RNA structures, while 25% of the events destabilized the secondary structure. Conclusions: We have developed a comprehensive framework to estimate consequence of RNA editing events at single-cell resolution. Our results demonstrate the power of our framework in elucidating the impact of RNA editing on cellular processes. Synonymous RNA editing expands our understanding of the complexity of genetic regulation and its implications for cellular processes and disease.