A computational screen implicating A-to-I editing as a key mechanism in fine-tuning proteome diversity
by
Örjan Åkerborg(SBC)
→
Europe/Stockholm
RB35
RB35
Description
Several bioinformatic approaches have previously been used to find novel sites of Adar mediated A-to-I editing in human. These studies have resulted in the discovery of thousands of genes hyper-edited in their non-coding regions but very few substrates that are site selectively edited. We have compiled a screen to search for new sites of selective editing primarily in coding sequences. To avoid hyper-edited repeat regions we have applied our screen to the alu-free mouse genome. First we construct an explorative screen based on RNA structure and genomic sequence conservation. We evaluate the explorative screen by means of enrichment of A-G mismatch, that is, the discrepancy between the expressed sequence and the genomic template for A-to-I edited sites. The enrichment and the corresponding p-values implicate A-to-I editing as a key mechanisms in fine tuning proteome diversity. Known substrates suggest that A-to-I editing is particularly important for normal brain development in mammals. Subsequently, we extend the explorative screen by including A-G mismatch as well as a specific scoring scheme based on characteristics for known A-to-I edited sites. The result of applying our extended screen to the mouse genome gives a substantial number of novel putative substrates of which 63 are currently experimentally validated.
