Abstract

BackgroundRNA editing by ADAR (adenosine deaminase acting on RNA) proteins is a form of transcriptional regulation that is widespread among humans and other primates. Based on high-throughput scans used to identify putative RNA editing sites, ADAR appears to catalyze a substantial number of adenosine to inosine transitions within repetitive regions of the primate transcriptome, thereby dramatically enhancing genetic variation beyond what is encoded in the genome.ResultsHere, we demonstrate the editing potential of the pig transcriptome by utilizing DNA and RNA sequence data from the same pig. We identified a total of 8550 mismatches between DNA and RNA sequences across three tissues, with 75% of these exhibiting an A-to-G (DNA to RNA) discrepancy, indicative of a canonical ADAR-catalyzed RNA editing event. When we consider only mismatches within repetitive regions of the genome, the A-to-G percentage increases to 94%, with the majority of these located within the swine specific SINE retrotransposon PRE-1. We also observe evidence of A-to-G editing within coding regions that were previously verified in primates.ConclusionsThus, our high-throughput evidence suggests that pervasive RNA editing by ADAR can exist outside of the primate lineage to dramatically enhance genetic variation in pigs.

Highlights

  • IntroductionRNA editing by Adenosine deaminase acting on RNA (ADAR) (adenosine deaminase acting on RNA) proteins is a form of transcriptional regulation that is widespread among humans and other primates

  • RNA editing by Adenosine deaminase acting on RNA (ADAR) proteins is a form of transcriptional regulation that is widespread among humans and other primates

  • DNA and RNA sequencing To provide the materials needed for a transcriptomewide survey of RNA editing candidates, genomic DNA as well as total RNA from liver, subcutaneous fat, and longissimus dorsi (LD) muscle were purified from samples obtained from a single animal, similar to another single-animal editome study [8]

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Summary

Introduction

RNA editing by ADAR (adenosine deaminase acting on RNA) proteins is a form of transcriptional regulation that is widespread among humans and other primates. Eukaryotes are known for relatively complex mechanisms used to regulate gene expression. One such mechanism, RNA editing, enables the cell to alter sequences of RNA transcripts [1] such that they are no longer forced to match the “hard-wired” genome sequence. High throughput methods for studying targets of this mechanism transcriptome-wide have been applied to primate studies, where evidence for massive amounts of ADAR (adenosine deaminase acting on RNA) catalyzed A-to-I RNA editing has been discovered, preferentially within SINE retrotransposons such as the primate Alu [2,3,4,5,6,7,8].

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