New research led by Joshua Rosenthal, PhD, of the Marine Biological Laboratory (MBL) and Eli Eisenberg, PhD, at Tel Aviv University, has revealed that octopuses and their close relatives adjust to environmental challenges by editing their RNA. Could these new findings provide insights into RNA editing for treating diseases in humans?

“We generally think that our genetic information is fixed, but the environment can influence how you encode proteins, and in cephalopods this happens on a massive scale,” explained Rosenthal.

The cephalopod study is published in Cell in an article titled, “Temperature-dependent RNA editing in octopus extensively recodes the neural proteome.”

“In poikilotherms, temperature changes challenge the integration of physiological function. Within the complex nervous systems of the behaviorally sophisticated coleoid cephalopods, these problems are substantial,” the researchers wrote. “RNA editing by adenosine deamination is a well-positioned mechanism for environmental acclimation. We report that the neural proteome of Octopus bimaculoides undergoes massive reconfigurations via RNA editing following a temperature challenge. Over 13,000 codons are affected, and many alter proteins that are vital for neural processes.”

Previous studies reported by GEN have shown how complex an octopus brain can be and the commonalities to those of humans. The current study documents an enormous uptick in RNA editing when octopus, squid, and cuttlefish, known as coleoid cephalopods, acclimate to cold water. After cooling the octopuses’ tanks, the team saw increases in protein-altering activity at more than 13,000 RNA sites in the animals’ nervous systems. In two of these cases, they investigated how swapping out a single letter of the RNA molecules’ code alters the function of proteins the neurons produce.

“We’re used to thinking all living things are preprogrammed from birth with a certain set of instructions,” Rosenthal said. “The idea the environment can influence that genetic information, as we’ve shown in cephalopods, is a new concept.”

The team collaborated with researchers at the University of Michigan and Texas Tech University, and investigated how RNA editing tweaked the function of two proteins that are vital for neural function in the octopuses. The first protein, kinesin-1, ferries cargo along the long branches of neurons. RNA editing, they found, changes the rate at which this molecule travels. Likewise, it alters the responsiveness of a protein called synaptotagmin that enables communication between neurons.

Cephalopods may use this form of genetic tinkering to adjust to change in many ways, well beyond acclimating to cold water, Rosenthal suspects. “I think it’s the tip of the iceberg,” he said of this study’s findings.

RNA editing has been implicated in various disorders including cancer and neurological diseases of the brain or the central nervous system. RNA editing holds promise for therapies for cancer, pain, high cholesterol, and genetic disorders.

Rosenthal and Eisenberg are working on a grant project from the National Institutes of Health to see if RNA editing can be used as a nonaddictive treatment for opioids.

The study not only opens the door to a deeper understanding of RNA editing in cephalopods, but may influence future studies and the development of new tools for RNA applications in humans.

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