Unexplored Opportunities in the Cardiovascular System
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Increasing usage of next-generation sequencing technology will illuminate the extent of RNA modifications, which may affect various pathophysiological conditions. Here, we will highlight one such category of RNA modification called RNA editing, which can be detected from RNA sequencing data by simply modifying the data analysis pipeline using bioinformatics methods.
Life on our planet depends on RNA. Despite our early understanding of RNA as an enabling messenger, it is not simply a static reflection of genetic activation. Indeed, the life span of RNA is more complex than previously thought. On transcription from the DNA template, RNA can be modified by various enzymes, which results in over 100 RNA modifications. Because of the potential involvement of RNA modifications in a variety of pathophysiologies, epitranscriptomics is quickly gaining momentum, and our gaps in understanding epitranscriptomics require further study.1
RNA editing is a post-transcriptional modification to alter the sequence of RNA molecules.2 RNA editing of exons of protein-coding genes may lead to the production of an amino acid sequence that differs from the original DNA sequence. In addition, editing of 3′-untranslated regions may affect binding of RBPs (RNA-binding proteins) or microRNAs (miRNAs), thereby modulating RNA stability or translation. There are 2 types of RNA editing: adenosine to inosine (A-to-I) and cytidine to uridine (C-to-U); A-to-I is the more common form. Furthermore, RNA editing can be identified in RNA sequencing (RNA-seq) data without any special treatment before the sequencing library construction. A-to-I RNA editing occurs through RNA-editing enzymes called ADARs (adenosine deaminases acting on RNA), which convert adenosine in double-stranded RNA into inosine. In humans, there are 3 ADARs (ADAR1, ADAR2, and ADAR3). In mice, the deletion of Adar1 and Adar2 (also known as Adarb1 [adenosine deaminase, RNA-specific, B1]) is embryonically and postnatally lethal, respectively,3,4 highlighting …