A novel computational strategy to identify A-to-I RNA editing sites by RNA-Seq data: de novo detection in human spinal cord tissue

PLoS One. 2012;7(9):e44184. doi: 10.1371/journal.pone.0044184. Epub 2012 Sep 5.

Abstract

RNA editing is a post-transcriptional process occurring in a wide range of organisms. In human brain, the A-to-I RNA editing, in which individual adenosine (A) bases in pre-mRNA are modified to yield inosine (I), is the most frequent event. Modulating gene expression, RNA editing is essential for cellular homeostasis. Indeed, its deregulation has been linked to several neurological and neurodegenerative diseases. To date, many RNA editing sites have been identified by next generation sequencing technologies employing massive transcriptome sequencing together with whole genome or exome sequencing. While genome and transcriptome reads are not always available for single individuals, RNA-Seq data are widespread through public databases and represent a relevant source of yet unexplored RNA editing sites. In this context, we propose a simple computational strategy to identify genomic positions enriched in novel hypothetical RNA editing events by means of a new two-steps mapping procedure requiring only RNA-Seq data and no a priori knowledge of RNA editing characteristics and genomic reads. We assessed the suitability of our procedure by confirming A-to-I candidates using conventional Sanger sequencing and performing RNA-Seq as well as whole exome sequencing of human spinal cord tissue from a single individual.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / genetics
  • Algorithms
  • Brain / metabolism
  • Computational Biology / methods
  • Databases, Genetic
  • Exome
  • Gene Expression Regulation
  • Genome, Human
  • Genomics
  • Homeostasis
  • Humans
  • Inosine / genetics
  • Neurodegenerative Diseases / metabolism
  • RNA Editing*
  • Reproducibility of Results
  • Software
  • Spinal Cord / metabolism
  • Spinal Cord / pathology*
  • Transcriptome

Substances

  • Inosine
  • Adenosine

Grant support

This work was supported by “Ministero dell’Istruzione, Università e Ricerca” (MIUR, Italy): “Laboratorio Internazionale di Bioinformatica”, “Laboratorio di Bioinformatica per la Biodiversità Molecolare” (Project DM19410), “PRIN 2009”; Consiglio Nazionale delle Ricerche: Flagship Project “Epigen”, PNR-CNR Aging Program 2012–2014, the Center of Excellence in Genomics (CEGBA, Italy), Italian Research Foundation for amyotrophic lateral sclerosis (AriSLA), and by Italian Ministry for Foreign Affairs (Italy-Israel actions). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.