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. 2012;7(3):e33720.
doi: 10.1371/journal.pone.0033720. Epub 2012 Mar 20.

Canonical A-to-I and C-to-U RNA editing is enriched at 3'UTRs and microRNA _target sites in multiple mouse tissues

Tongjun Gu  1 , Frank W Buaas, Allen K Simons, Cheryl L Ackert-Bicknell, Robert E Braun, Matthew A Hibbs
Affiliations

Canonical A-to-I and C-to-U RNA editing is enriched at 3'UTRs and microRNA _target sites in multiple mouse tissues

Tongjun Gu et al. PLoS One. 2012.

Abstract

RNA editing is a process that modifies RNA nucleotides and changes the efficiency and fidelity of the central dogma. Enzymes that catalyze RNA editing are required for life, and defects in RNA editing are associated with many diseases. Recent advances in sequencing have enabled the genome-wide identification of RNA editing sites in mammalian transcriptomes. Here, we demonstrate that canonical RNA editing (A-to-I and C-to-U) occurs in liver, white adipose, and bone tissues of the laboratory mouse, and we show that apparent non-canonical editing (all other possible base substitutions) is an artifact of current high-throughput sequencing technology. Further, we report that high-confidence canonical RNA editing sites can cause non-synonymous amino acid changes and are significantly enriched in 3' UTRs, specifically at microRNA _target sites, suggesting both regulatory and functional consequences for RNA editing.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Distribution and validation of editing sites observed in RNA-seq data.
A) Distribution of RNA editing types with and without a filter for significant strand bias from RNA-seq data. B,C) RNA-seq traces are shown for one canonical RNA editing site (C-to-U in Serinc1) and for one non-canonical editing site (G-to-C in Lars2). Reads sequenced in the sense direction are shown in dark grey, while reads sequenced in the reverse direction are shown in light grey. D,E) Sanger sequencing validation results for sites in Serinc1 and Lars2. F,G) RFLP validation of sites in Serinc1 and Lars2. Samples exposed to enzyme are labeled “en+” and control samples are labeled “en-.” H) Genomic distribution of editing sites and random background.
Figure 2
Figure 2. Identification of high-confidence RNA editing sites.
A) Distribution of editing ratio for all observed canonical and non-canonical RNA editing sites in our adipose RNA-seq data shows that the ratio is higher for non-canonical than canonical sites. B) Distribution of Fisher's exact test p-values for strand bias. Non-canonical RNA editing sites shows an extreme peak around zero, indicating that most non-canonical RNA editing sites are supported by strand biased reads. C) Overview of our RNA editing analysis pipeline.
Figure 3
Figure 3. Example of RNA editing at microRNA _target sites.
One hundred nucleotides of the 3′UTR of Rpa1 is shown. Multiple microRNA _target sites form a dense cluster in this region and contain many A-to-I editing sites. Red bases represent RNA editing sites, and blue and green bases represent different microRNA seed locations.
See this image and copyright information in PMC

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