Email updates

Keep up to date with the latest news and content from Genome Biology and BioMed Central.

Open Access Highly Accessed Research

Alu elements shape the primate transcriptome by cis-regulation of RNA editing

Chammiran Daniel1, Gilad Silberberg2, Mikaela Behm1 and Marie Öhman1*

Author Affiliations

1 Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden

2 Present address: Unit of Computational Medicine, Center for Molecular Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden

For all author emails, please log on.

Genome Biology 2014, 15:R28  doi:10.1186/gb-2014-15-2-r28

Published: 3 February 2014

Abstract

Background

RNA editing by adenosine to inosine deamination is a widespread phenomenon, particularly frequent in the human transcriptome, largely due to the presence of inverted Alu repeats and their ability to form double-stranded structures – a requisite for ADAR editing. While several hundred thousand editing sites have been identified within these primate-specific repeats, the function of Alu-editing has yet to be elucidated.

Results

We show that inverted Alu repeats, expressed in the primate brain, can induce site-selective editing in cis on sites located several hundred nucleotides from the Alu elements. Furthermore, a computational analysis, based on available RNA-seq data, finds that site-selective editing occurs significantly closer to edited Alu elements than expected. These targets are poorly edited upon deletion of the editing inducers, as well as in homologous transcripts from organisms lacking Alus. Sequences surrounding sites near edited Alus in UTRs, have been subjected to a lesser extent of evolutionary selection than those far from edited Alus, indicating that their editing generally depends on cis-acting Alus. Interestingly, we find an enrichment of primate-specific editing within encoded sequence or the UTRs of zinc finger-containing transcription factors.

Conclusions

We propose a model whereby primate-specific editing is induced by adjacent Alu elements that function as recruitment elements for the ADAR editing enzymes. The enrichment of site-selective editing with potentially functional consequences on the expression of transcription factors indicates that editing contributes more profoundly to the transcriptomic regulation and repertoire in primates than previously thought.