How do octopuses edit their own RNA?

Octopuses, squid and cuttlefish edit their messenger RNA using ADAR enzymes. These enzymes chemically change the base adenosine into inosine. Ribosomes read inosine as guanine, so the protein built from the message can differ from what the DNA specifies. The DNA itself stays the same. Coleoid cephalopods do this on a scale not seen in other known animals. [1] [2]

Normally, DNA is copied into mRNA, and ribosomes read the mRNA to string amino acids into a protein. In A-to-I editing, an ADAR enzyme acts on double-stranded RNA and removes a nitrogen and two hydrogen atoms from adenosine, turning it into inosine. Because inosine pairs like guanosine, ribosomes treat it as a G. Sometimes the swap makes no difference to the protein. In other cases it puts a different amino acid into the chain, which is called RNA recoding. Researchers compare recoding to an A-to-G mutation, except that it happens in the RNA and leaves the DNA unchanged. [1] [2]

A review in Briefings in Functional Genomics reports close to 100,000 editing sites in protein-coding regions in the brains of several coleoids. Nautilus and sea slugs have roughly 1,000, similar to estimates for humans. Close to 60 percent of squid, cuttlefish and octopus brain transcripts contain at least one recoding site. Many of the edited messages encode proteins important to nervous system function, such as ion channels, transporters and the machinery for releasing synaptic vesicles. [2]

Science News reports one possible contributor: most animals edit RNA in the nucleus, but cephalopods also have ADAR2 in the cytoplasm, which may give more opportunities for editing. The review notes, however, that how the ADAR enzymes produce so many recoding events is still poorly understood. Most animals have two active enzymes, ADAR1 and ADAR2, and their counterparts in other groups produce only a few hundred recoding sites. [1] [2]

A study of Octopus bimaculoides moved wild-caught animals to water at about 13 or 22 degrees Celsius. Of 62,661 well-covered editing sites in the stellate ganglia, about 33 percent had significantly higher editing in the cold, and only about 1 percent had higher editing in the warm. More than 13,000 codons were affected. In two examples, editing changed protein behavior: in synaptotagmin it altered calcium binding, and in kinesin-1 it changed transport velocity along microtubules. Seasonal sampling of wild animals suggested the same temperature-dependent editing happens in nature. [3]

The authors conclude that editing tunes neural function to temperature in octopus and likely other coleoids. Edits are also not all-or-nothing, since they can occur in only some of the copies of an RNA, unlike a change in DNA. [3]