Overview of ADAR localization and function. (a) Transgenic HA-tagged ADAR (green) localizes within the nuclear envelope (lamin, red) and more specifically to the nucleolus (fibrillarin, red) in Drosophila salivary gland cells. (b) Endogenous HA-tagged ADAR (green) localizes to the Drosophila neuronal nucleus and colocalizes with the nucleolus, distinguished by the red fibrillarin signal (arrowheads). (c) RNA structures that direct editing. The complex pseudoknot of Drosophila synaptotagmin-I is presented in contrast with the simple hairpin of mammalian GluR-2, both specific editing targets. Exons are represented in blue, introns in black. Adenosines targeted by ADAR are red. (d) Editing affects splicing. Mammalian ADAR2 auto-edits its own transcript, creating a novel splice site (red), which results in the inclusion of 47 nucleotides (yellow) and a frameshift in the coding sequence. In the mammalian GluR-2 transcript, editing at both the Q/R site in exon 11 and an intronic 'hotspot' (red) is required for efficient removal of the downstream intron. Editing of the R/G site (red) reduces efficacy of downstream splicing and favors an alternative final exon configuration (yellow). (e) Editing can interfere with siRNA and microRNA production and targeting. Perfectly duplex siRNA precursors are targets for hyper-editing by ADARs. Editing may result in improper Dicer processing and fewer functional siRNAs, or edited siRNAs. Primary (pri) microRNAs, imperfect duplexes, may be targets for specific editing, resulting in mature miRNAs toward alternative mRNA targets.
Savva et al. Genome Biology 2012 13:252 doi:10.1186/gb-2012-13-12-252