Abstract

BackgroundRecent studies have revealed thousands of A-to-I RNA editing events in primates, but the origination and general functions of these events are not well addressed.ResultsHere, we perform a comparative editome study in human and rhesus macaque and uncover a substantial proportion of macaque A-to-I editing sites that are genomically polymorphic in some animals or encoded as non-editable nucleotides in human. The occurrence of these recent gain and loss of RNA editing through DNA point mutation is significantly more prevalent than that expected for the nearby regions. Ancestral state analyses further demonstrate that an increase in recent gain of editing events contribute to the over-representation, with G-to-A mutation site as a favorable location for the origination of robust A-to-I editing events. Population genetics analyses of the focal editing sites further reveal that a portion of these young editing events are evolutionarily significant, indicating general functional relevance for at least a fraction of these sites.ConclusionsOverall, we report a list of A-to-I editing events that recently originated through G-to-A mutations in primates, representing a valuable resource to investigate the features and evolutionary significance of A-to-I editing events at the population and species levels. The unique subset of primate editome also illuminates the general functions of RNA editing by connecting it to particular gene regulatory processes, based on the characterized outcome of a gene regulatory level in different individuals or primate species with or without these editing events.

Highlights

  • RNA editing is a post-transcriptional mechanism that introduces differences between RNA and its corresponding DNA sequence [1]

  • Due to the prevalence of dsRNA structures formed by the inverted repeated Alus in primates, which are the preferred substrates of ADARs, A-to-I editing is the most common type of RNA editing in primates [2]

  • Recent gain and loss of Alu-associated A-to-I RNA editing through DNA mutation in rhesus macaque To study the recent gain and loss of RNA editing in primates, we used rhesus macaque as a model animal and profiled the RNA editome in six tissues of the same macaque animal (Fig. 1a)

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Summary

Introduction

RNA editing is a post-transcriptional mechanism that introduces differences between RNA and its corresponding DNA sequence [1]. Most A-to-I RNA editing sites in primates are contributed by the expansion of primate-specific Alu elements [6, 7]. Of these widespread A-to-I RNA editing sites in primates, only a small proportion is located in well-recognized functional regions, such as the protein-coding or miRNA encoding loci, and presumably implicated in altering sequences of proteins or miRNAs [1, 3, 5, 8, 9]. Recent studies have revealed thousands of A-to-I RNA editing events in primates, but the origination and general functions of these events are not well addressed

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