Genome-wide analysis of Alu editability

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Abstract

A-to-I RNA editing is apparently the most abundant post-transcriptional modification in primates. Virtually all editing sites reside within the repetitiveAluSINEs.Alusequences are the dominant repeats in the human genome and thus are likely to pair with neighboring reversely oriented repeats and form double-stranded RNA structures that are bound by ADAR enzymes. Editing levels vary considerably between different adenosine sites withinAlurepeats. Part of the variability has been explained by local sequence and structural motifs. Here, we focus on global characteristics that affect the editability at theAlulevel. We use large RNA-seq data sets to analyze the editing levels in 203 798Alurepeats residing within human genes. The most important factor affectingAlueditability is its distance to the closest reversely oriented neighbor—average editability decays exponentially with this distance, with a typical distance of ∼800 bp. This effect alone accounts for 28% of the total variance in editability. In addition, the number ofAlurepeats of the same and reverse strand in the genomic vicinity, the expressed strand of theAlu,Alu’s length and subfamily and the occurrence of reversely oriented neighbor in the same intron\exon all contribute, to a lesser extent, to theAlueditability.

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