Friday, September 18

Squid edit their genetic material in a uniquely weird place

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.”