Spatially regulated editing of genetic information within a squid neuron

In eukaryotic cells, with the exception of the specialized genomes of mitochondria and plastids, all genetic information is sequestered within the nucleus. This arrangement imposes constraints on how the information can be tailored for different cellular regions, particularly in cells with complex morphologies like neurons. Although messenger RNAs, and the proteins that they encode, can be differentially sorted between cellular regions, the information itself does not change. RNA editing by adenosine deamination can alter the genome's blue-print by recoding mRNAs, however this process too is thought to be restricted to the nucleus. In this work we show that ADAR2 (Adenosine Deaminases that Act on RNA), an RNA editing enzyme, is expressed outside of the nucleus in squid neurons. Furthermore, purified axoplasm exhibits adenosine-to-inosine activity and can specifically edit adenosines in a known substrate. Finally, a transcriptome-wide analysis of RNA editing reveals that tens of thousands of editing sites are edited more extensively in the squid giant axon than its cell bodies. These results indicate that within a neuron RNA editing can recode genetic information in a region-specific manner.