Squid Can Control Their Genetic Coding By Editing Their RNA

The longfin inshore squid, Doryteuthis pealeii, long-established as a research organism for fundamental biological studies. Elaine Bearer

Rachael Funnell 26 Mar 2020, 10:09

A new study published in Nucleic Acids Research has found that squids have the ability to change what their genes code for by tweaking their RNA after it leaves the nucleus. This amazing capability allowing the squids to cater the proteins they produce at local sites has never been observed in another animal.

In typical human reproduction, babies are born with either an XX or XY karyotype made up of a blend of their parents’ DNA. These inherited genes code for everything in the body, from hair color to organ function. Our genes are cemented and while certain mechanisms can alter their expression, often triggering the onset of disease, they will remain unchanged throughout our life.

The same rigidity applies to messenger RNA (mRNA), which are employed in the cell to read short sections of our DNA so that they can code for proteins. Once an mRNA has “transcribed” its section of DNA, it leaves the cell nucleus to begin building. It was once thought that uniformly across the animal kingdom, once that mRNA had left the cell nucleus no further edits could be made to the transcription taken from the DNA, but now, thanks to squids, we know that is not true.

“[W]e thought all the RNA editing happened in the nucleus, and then the modified messenger RNAs are exported out to the cell," said Joshua Rosenthal, senior author of the study, in a statement. "Now we are showing that squid can modify the RNAs out in the periphery of the cell. That means, theoretically, they can modify protein function to meet the localized demands of the cell. That gives them a lot of latitude to tailor the genetic information, as needed."

Top, schematic of squid anatomy showing the location of the "giant axon". Below, schematic of a neuron, showing the location of the nucleus where all RNA editing was previously thought to occur, and the axon, where local RNA editing was identified in squid. Vallecillo-Viejo et al, Nucl. Acids Res., 2020.

The team who made the discovery were investigating nerves from adult male Doryteuthis pealeii, the longfin inshore squid and the expression of the squid’s transcriptome. A transcriptome is the set of all RNA molecules in one cell, sort of like the genome but made up of mRNA. It was observed that the mRNA of the squid’s neurons was being edited in the axon, which is the long filament of a nerve cell along which carries impulses from the cell body to other cells.

The capacity to edit the mRNA outside of the nucleus enables the squid to alter which proteins are expressed (coded for) along different parts of the nervous system. The team isn’t yet sure exactly why squid have evolved this capability, which implies it plays a beneficial role. mRNA editing within the nucleus has been observed in octopus and cuttlefish, which has led to researchers questioning if perhaps this tweaking skill has contributed to these invertebrates' superior intelligence. The link remains unclear but Rosenthal highlights that, "RNA editing is a hell of a lot safer than DNA editing. If you make a mistake, the RNA just turns over and goes away."

The study still has some way to go in understanding the exact purpose and mechanism of the unique mRNA editing in squid, but it’s hoped the research could one day contribute to better understanding and treating neurological disorders that center around axon dysfunction. If we were able to edit RNA within our cells, it would be much safer than novel treatments that currently use CRISPR to edit our DNA.

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