Squid can edit their genetic information in a place scientists didn’t expect.
Longfin inshore squid (Doryteuthis pealeii) are the first known animals that can tweak strings of RNA outside of a nerve cell’s nucleus. These genetic couriers, called messenger RNA, or mRNA, carry a cell’s blueprints for building proteins.
All creatures make edits to RNA — including other types besides mRNA — and do so sparingly, based on limited studies in mammals and fruit flies. Those changes typically take place inside the nucleus and are then exported to the rest of the cell.
The squids’ ability to make genetic edits in cytoplasm, the jellylike material that makes up much of a cell, may let the animals make adjustments to mRNAs on the fly. That skill could help squids produce proteins tailored to meet a cell’s needs and hone crucial cell processes, researchers report March 23 in Nucleic Acids Research.
Knowing how the squids make the edits in nerve cells could help researchers hijack the technique to develop therapeutics for health conditions such as chronic pain by genetically editing cells that create inappropriate pain signals, says Joshua Rosenthal, a biologist at the Marine Biological Laboratory in Woods Hole, Mass. The method would be much like the DNA-editing technique CRISPR, but for RNA.
In the new study, Rosenthal and colleagues first looked at where an mRNA-editing protein is found in squid nerve cells, or neurons. The team discovered that the protein, called ADAR2, is located in both the jellylike cytoplasm and the nucleus of squid neurons, a hint that the protein could edit mRNAs in both areas.
The team then extracted cytoplasm from squid axons — the slender stalk of a neuron — “kind of like you’re squeezing toothpaste out of the tube,” Rosenthal says. ADAR2 extensively edited an mRNA within the cytoplasm siphoned from the axons, which help send electrical impulses along nerve cells, the researchers found.
Developing an RNA-editing technique similar to CRISPR could come with key advantages. While CRISPR-generated edits in DNA are permanent, RNA is transient, and edited genetic information would disappear when the RNA is broken down in the cell (SN: 10/25/17).
“There are a lot of advantages for trying to manipulate genetic information in RNA,” Rosenthal says. “If you make a mistake, it’s not nearly so dangerous. If you make mistakes in DNA, you’re stuck with it.”