© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Vallecillo-Viejo, I. C., Liscovitch-Brauer, N., Diaz Quiroz, J. F., Montiel-Gonzalez, Maria F., Nemes, Sonya E., Rangan, K. J., Levinson, S. R., Eisenberg, E., & Rosenthal, J. J. C. Spatially regulated editing of genetic information within a neuron. Nucleic Acids Research, (2020): gkaa172, doi: 10.1093/nar/gkaa172.
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 (mRNAs), 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 blueprint by recoding mRNAs; however, this process too is thought to be restricted to the nucleus. In this work, we show that ADAR2 (adenosine deaminase that acts 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 (〉70% of all sites) are edited more extensively in the squid giant axon than in its cell bodies. These results indicate that within a neuron RNA editing can recode genetic information in a region-specific manner.
National Science Foundation (NSF) [IOS1557748 to J.R.]; United States–Israel Binational Science Foundation [BSF2013094 to J.R. and E.E.]; The Grass Foundation grant in support of the Doryteuthis pealeii Genome Project, and a gift by Mr. Edward Owens. Funding for open access charge: United States–Israel Binational Science Foundation [BSF2013094].
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