In recent years, a spirited debate has taken place on the topic of RNA editing, a process in which (classically) proteins of the ADAR family edit adenosine bases in RNA to inosine. The most hotly contested topics are: How prevalent is RNA editing in mammalian cells? And, are there additional, more exotic editing varieties than the canonical A-to-I switch? However, answering these questions won’t solve a key evolutionary question. As with many components of RNA metabolism, such as introns, it is intriguing that the cell finds RNA editing to be worthwhile at all. Why go to the bother of editing RNA when a simple base substitution at the DNA level would have the same effect?
A new study in Genome Biology’s RBPome issue by Erez Levanon and colleagues from Bar-Ilan University, Israel, adds a twist to the puzzle, with a measurement of RNA editing sites that are conserved between human and mouse. The number? Just 59.
Assuming that conservation serves as an approximation for ‘essential function’, it is remarkable that so few mammalian RNA editing sites appear to be essential. But given that it seems the transcriptome is quite relaxed about letting most sites waste away, a perhaps more interesting question to ask is what is so special about this select set of 59 sites, that they are preserved?
This question brings to mind a recent study that found that RNA editing allows an octopus to adapt its K+ channels to different sea temperatures. Levanon and colleagues noticed that the elite RNA editing sites shared between human and mouse tended to be located in genes encoding neurotransmitter receptors or other synapse related proteins. Could it be that synapses have coopted RNA editing as a mechanism to adapt their constituent proteins to different environmental or developmental conditions?
Numerous adaptations at the protein level, such as phosphorylation, have been well characterized as mechanisms by which the cell can respond to changing conditions. A similar purpose of the epigenome is the focus of intensive study. RNA editing is one of several strategies the cell may use to achieve the same goal by remodeling the transcriptome – but these strategies are in general not yet well understood. Genome Biology’s RBPome issue aims to shed light on evolution’s affection for the protein-based reshaping of the transcriptome as an agent of dynamic adaptation, whether by editing, splicing, stabilizing or degrading.