The majority of transcripts in the squid nervous system are extensively recoded by A-to-I RNA editing
Shahar Alon,
Sandra C Garrett,
Erez Y Levanon,
Sara Olson,
Brenton R Graveley,
Joshua J C Rosenthal,
Eli Eisenberg
Affiliations
Shahar Alon
George S Wise Faculty of Life Sciences, Department of Neurobiology, Tel Aviv University, Tel Aviv, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
Sandra C Garrett
Department of Genetics and Developmental Biology, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, United States
Erez Y Levanon
Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
Sara Olson
Department of Genetics and Developmental Biology, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, United States
Brenton R Graveley
Department of Genetics and Developmental Biology, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, United States
Joshua J C Rosenthal
Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
Eli Eisenberg
Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel; Raymond and Beverly Sackler School of Physics and Astronomy, Tel Aviv University, Tel Aviv, Israel
RNA editing by adenosine deamination alters genetic information from the genomic blueprint. When it recodes mRNAs, it gives organisms the option to express diverse, functionally distinct, protein isoforms. All eumetazoans, from cnidarians to humans, express RNA editing enzymes. However, transcriptome-wide screens have only uncovered about 25 transcripts harboring conserved recoding RNA editing sites in mammals and several hundred recoding sites in Drosophila. These studies on few established models have led to the general assumption that recoding by RNA editing is extremely rare. Here we employ a novel bioinformatic approach with extensive validation to show that the squid Doryteuthis pealeii recodes proteins by RNA editing to an unprecedented extent. We identify 57,108 recoding sites in the nervous system, affecting the majority of the proteins studied. Recoding is tissue-dependent, and enriched in genes with neuronal and cytoskeletal functions, suggesting it plays an important role in brain physiology.
