Squids' Gene-Editing Superpowers May Unlock Human Cures

Gene-editing techniques like Crispr-based technologies aim to cure human disease by altering the genetic code of our DNA. For nearly every animal on Earth, any changes made to the DNA are transmitted from the cell nucleus by messenger RNA to the cytoplasm, the part of the cell that makes proteins. But one animal species—a squid used as bait by fishermen, and as food by bigger sea creatures—has already figured out how to edit its genetic code in a way that may help scientists working on gene editing-based drugs and treatments. Scientists at the Marine Biological Laboratory in Woods Hole, Massachusetts, and their colleagues reported on Monday in the journal Nucleic Acids Research that longfin inshore squid (Doryteuthis pealeii) are the first known animals that can edit messenger RNA outside the cell nucleus.
MBL senior scientist Joshua Rosenthal, an author on the new paper, says this unusual method of editing messenger RNA likely has something to do with the squid’s behavior in the ocean. “It works by this massive tweaking of its nervous system,” Rosenthal adds. “Which is a really novel way of going through life.”All organisms do some form of RNA editing. In humans, some disorders have been linked to malfunctions of RNA editing, such as the sporadic form of amyotrophic lateral sclerosis, better known as ALS or Lou Gehrig's Disease. RNA editing also plays a role in immunity, and some studies in fruit flies show that it may help them adapt to changing temperatures.illustration of a tool chest with dna strands

The WIRED Guide to Crispr

A Doryteuthis pealeii But the squid does this RNA editing on a massive scale. More than 60,000 brain cells undertake this recoding process in squid, as compared with a few hundred sites in humans. Rosenthal and colleagues from Tel Aviv University and the University of Colorado at Denver found that RNA editing takes place in the squid’s axon, the stretched-out region of the brain cell that transmits electrical signals to nearby neurons. This is an important finding because squid nerve cells are immense, with axons sometimes stretching several feet long. By editing their RNA outside the nucleus, the squid can potentially change protein function much closer to the part of the body that needs an adaptation.
For Rosenthal, now that his team knows that the squid has the cellular machinery to do this RNA editing, the next task is to understand why. He suspects it has something to do with allowing the squid to better adapt to changing environmental conditions such as water temperature. “We want to look at its behavior if I manipulate the RNA editing,” he says.

Photograph: Roger Hanlon/The Marine Biological Laboratory