The majority of transcripts in the squid nervous system are extensively recoded by A-to-I RNA editing

For living cells to create a protein, a genetic code found in its DNA must first be ‘transcribed’ to create a corresponding molecule of messenger RNA (mRNA). DNA and RNA are both made from smaller molecules called nucleotides that are linked together into long chains; the information in both DNA and RNA is contained in the sequence of these molecules. The mRNA nucleotides coding for proteins are ‘translated’ in groups of three, and most of these nucleotide triplets instruct for a specific amino acid to be added to the newly forming protein. DNA sequences were thought to exactly correspond with the sequence of amino acids in the resulting protein. However, it is now known that processes called RNA editing can change the nucleotide sequence of the mRNA molecules after they have been transcribed from the DNA. One such editing process, called A-to-I editing, alters the ‘A’ nucleotide so that the translation machinery reads it as a ‘G’ nucleotide instead. In some—but not all—cases, this event will change, or ‘recode’, the amino acid encoded by this stretch of mRNA, which may change how the protein behaves. This ability to create a range of proteins from a single DNA sequence could help organisms to evolve new traits. Evidence of amino acid recoding has only been found to a very limited extent in the few species investigated so far. There has been some evidence that suggests that recoding might occur more often, and alter more proteins, in squids and octopuses. However, this could not be confirmed as the genomes of these species have not been sequenced, and these sequences were required to investigate RNA recoding using existing techniques. Alon et al. have now developed a new approach that allows the recoding sites to be identified in organisms whose genomes have not been sequenced. Using this technique—which compares mRNA sequences with the DNA sequence they have been transcribed from—to examine the squid nervous system revealed over 57,000 recoding sites where an ‘A’ nucleotide had been modified to ‘G’ and thereby changed the coded amino acid. Many of the identified mRNA molecules had been recoded in more than one place, and many more of these than expected changed the amino acid sequence of the protein translated from them. Alon et al. therefore suggest that RNA editing may have been crucial in the evolution of the squid's nervous system, and suggest that recoding should be considered a normal part of the process used by squids to make proteins.