As poikilotherms, invertebrates are at the mercy of the temperature environment. This must place constraints on their machinery for excitability: a collection learn more of ion pumps, ion channels, and neurotransmitter release components, all with slightly different temperature sensitivities. Being able to fine tune the individual components could prove highly useful. More genetic recoding by A-to-I editing has been uncovered in Drosophila
melanogaster than in any other organism to date. This is because a comparatively large effort has been spent on looking for editing sites in this model and the fact that, quite simply, Drosophila appears to edit a great deal. As with all systems, the first sites were discovered through serendipitous encounters, when astute investigators noticed guanosine residues in cDNA sequences at positions occupied by adenosine in the genome. One often wonders how many editing sites escaped discovery when such discrepancies were attributed to sequencing artifacts. Most of the early sites discovered in flies were in mRNAs encoding voltage-gated or ligand-gated ion channels. The completion of the Drosophila buy LGK-974 genome in 2000 enabled more sophisticated screens to be undertaken and soon close to 50 new transcripts were found
to be edited, many at multiple sites ( Hoopengardner et al., 2003 and Stapleton et al., 2006). Intriguingly, most of these transcripts encode proteins involved Linifanib (ABT-869) in electrical signaling. A recent effort by Graveley and colleagues, using high throughput sequencing to examine complete transcriptomes of 32 developmental stages from embryos to adults, has probably uncovered the majority of editing sites ( Graveley et al., 2011). In it, they report 972 editing sites in 597 mRNAs, representing ∼4% of all transcripts. Remarkably, about two-thirds of the sites change codons.
Of the rest, 201 are silent and 141 are in UTRs. Such a high bias toward recoding events suggests that editing is under selective pressure and therefore being used to actively regulate physiological processes. Close to a quarter of the editing sites are within mRNAs encoding proteins involved in the machinery for excitability (defined here as ion channels, ion transporters, and proteins involved in neurotransmitter release and recycling). However, mRNAs encoding proteins involved in other cellular functions (e.g., cytoskeletal architecture and protein phosphorylation) are edited as well. This study is an exceptionally important addition to the field of RNA editing. It should enable the investigator to move beyond editing site identification and begin to address fundamental questions on the biology of the process. In spite of the abundance of editing sites that have been identified in Drosophila, very little is known about how they affect protein function, and in no cases are the mechanistic underpinnings of their effects understood.