Discriminative Prediction of A-To-I RNA Editing Events from DNA Sequence.

Jiangming Sun,Peter Spégel,Hindrik Mulder,Petter Vikman,Pratibha Singh,Bérengère Valtat,Peter Osmark,Annika Bagge,Yang De Marinis,Quan Zou

doi:10.1371/journal.pone.0164962

Abstract

RNA editing is a post-transcriptional alteration of RNA sequences that, via insertions, deletions or base substitutions, can affect protein structure as well as RNA and protein expression. Recently, it has been suggested that RNA editing may be more frequent than previously thought. A great impediment, however, to a deeper understanding of this process is the paramount sequencing effort that needs to be undertaken to identify RNA editing events. Here, we describe an in silico approach, based on machine learning, that ameliorates this problem. Using 41 nucleotide long DNA sequences, we show that novel A-to-I RNA editing events can be predicted from known A-to-I RNA editing events intra- and interspecies. The validity of the proposed method was verified in an independent experimental dataset. Using our approach, 203 202 putative A-to-I RNA editing events were predicted in the whole human genome. Out of these, 9% were previously reported. The remaining sites require further validation, e.g., by targeted deep sequencing. In conclusion, the approach described here is a useful tool to identify potential A-to-I RNA editing events without the requirement of extensive RNA sequencing.

Highlights

RNA editing is a post-transcriptional processing of the RNA molecule, involving insertions and deletions of bases, as well as base substitutions
The second is A-to-I editing, where adenosine is deaminated to inosine by the adenosine deaminases acting on RNA (ADAR) family of enzymes; this is the predominating type of RNA editing
We made a descriptive analysis using the Darned database [19] (Fig 2). This analysis revealed that A-to-I RNA editing events were most frequent in introns, followed by regions that were neither introns nor exons or 3’ untranslated regions (3’ UTR) in both mice and humans

Summary

Introduction

RNA editing is a post-transcriptional processing of the RNA molecule, involving insertions and deletions of bases, as well as base substitutions. Two types of RNA editing have been described in mammals. The first is C-to-U editing catalyzed by the apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family of enzymes; its frequency is quite low. The second is A-to-I editing, where adenosine is deaminated to inosine by the adenosine deaminases acting on RNA (ADAR) family of enzymes; this is the predominating type of RNA editing. In 2011, widespread differences between human RNA and DNA sequences were found [5]. From this finding, the existence of a PLOS ONE | DOI:10.1371/journal.pone.0164962. The existence of a PLOS ONE | DOI:10.1371/journal.pone.0164962 October 20, 2016

Methods

Results

Conclusion