NEW YORK (GenomeWeb) – A team from Israel, the US, and Puerto Rico has demonstrated that a subclass of invertebrate animals such as octopuses, squid, and cuttlefish frequently turn to RNA editing to adjust or tweak the proteins produced from their genes.
"Basically, this is a mechanism to make proteins that are not encoded in the DNA. They are not present in the genomic sequence," co-corresponding author Eli Eisenberg, a biophysics and neuroscience researcher at Tel Aviv University, said in a statement. "With these cephalopods, this is not the exception. This is the rule. The rule is that most of the proteins are being edited."
Eisenberg and his colleagues followed on past research that implicated RNA editing as a mechanism for altering protein outputs in the squid brain or in octopuses shifted from one environmental condition to another. They compared matched DNA and RNA sequences from four cephalopods in the coleoid subclass — the Octopus vulgaris and O. bimaculoides octopus species, the Doryteuthis pealeii squid, and the Sepia oficianalis cuttlefish — and two simpler cephalopods, a nautilus and a gastropod mollusk called the sea hare.
To gauge the prevalence of the RNA editing process in the coleoids — which are known for their complicated hunting and social behaviors — the researchers used Illumina HiSeq 2000 instruments to sequence DNA and RNA from the six animals. After weeding out DNA-RNA mismatches attributed to sequencing errors or sequence variants, the team was left with candidate RNA editing events that were validated and characterized in more detail with mass spectrometry-based proteomic profiling, RNA sequencing on a dozen cephalopod tissue types, functional experiments, and selection analyses.
As they reported online today in Cell, the researchers found that post-transcriptional regulation via RNA editing seems to affect a significant proportion of genes encoded by the coleoid invertebrates. The RNA editing was enhanced in nervous system tissue and for genes neighboring conserved sequences. From these and other findings, the researchers speculated that coleoid cephalopods may rely on extensive RNA editing as an alternative to genome evolution processes fueled by DNA base changes.
"We know there's a price [to RNA editing]. The price is slowing down genome evolution," Eisenberg said. "Cephalopods probably chose to take this RNA bargain over genome evolution, and maybe vertebrates made the other choice — they preferred genome evolution over editing."
Though RNA editing occurs relatively infrequently in vertebrate animals, there is mounting evidence that invertebrate animals in the cephalopod lineage are capable of swapping out adenosine bases and replacing them with inosine in messenger RNAs with enzymes that deaminate adenosine.
"Because inosine is recognized as guanosine during translation," the authors wrote, "this process has the capacity to recode codons and fine-tune protein function."
From their new analyses, the authors found that this process "is particularly common in behaviorally sophisticated coleoid cephalopods, with tens of thousands of evolutionary sites," though it remains to be seen how much of trademark shrewdness, dexterity, and social complexity attributed with the coleoids can be traced back to RNA editing.
"These behaviorally complex coleoids all have this tremendous RNA editing, particularly in their nervous system," co-corresponding author Joshua Rosenthal, a cephalopod neurobiology researcher affiliated with Woods Hole's Marine Biological Laboratory and the University of Puerto Rico, said in a statement. "RNA editing is an elegant system to add flexibility to your genetic information, but it's a real challenge to figure out when it's being used and how it's being used."