title: The majority of transcripts in the squid nervous system are extensively recoded by A-to-I RNA editing.
abstract: 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.
authors.affiliation: George S Wise Faculty of Life Sciences, Department of Neurobiology, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Shahar
authors.initials: S
authors.lastname: Alon
authors.affiliation: Department of Genetics and Developmental Biology, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, United States.
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Garrett
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Erez Y
authors.initials: EY
authors.lastname: Levanon
authors.affiliation: Department of Genetics and Developmental Biology, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, United States.
authors.forename: Sara
authors.initials: S
authors.lastname: Olson
authors.affiliation: Department of Genetics and Developmental Biology, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, United States.
authors.forename: Brenton R
authors.initials: BR
authors.lastname: Graveley
authors.affiliation: Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico.
authors.forename: Joshua J C
authors.initials: JJ
authors.lastname: Rosenthal
authors.affiliation: Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Eli
authors.initials: E
authors.lastname: Eisenberg
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D049832:Decapodiformes / Q000235:genetics*; D016678:Genome; D007288:Inosine / Q000378:metabolism*; D008969:Molecular Sequence Data; D009420:Nervous System / Q000378:metabolism*; D017393:RNA Editing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D000596:Amino Acids; D012333:RNA, Messenger; D007288:Inosine; D000241:Adenosine
keywords: Doryteuthis pealeii; RNA editing; evolutionary biology; genomics; neuroscience; recoding