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.
Highlights
The central dogma of biology maintains that genetic information passes faithfully from DNA to RNA to proteins; with the help of tools such as alternative splicing, organisms use RNA as a canvas to modify and enrich this flow of information
RNA editing by deamination of adenosine to inosine (A-to-I) is another process used to alter genetic information (Nishikura, 2010)
A-to-I RNA editing is catalyzed by the ADAR family of enzymes
Summary
The central dogma of biology maintains that genetic information passes faithfully from DNA to RNA to proteins; with the help of tools such as alternative splicing, organisms use RNA as a canvas to modify and enrich this flow of information. It should be noted that only annotated ORFs were examined in our pipeline, and the number of editing sites did not saturate with respect to the number of sequence reads (Figure 2—figure supplement 5).
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