The study, led by Isabel C. Vallecillo-Viejo and Joshua Rosenthal at
the Marine Biological Laboratory (MBL), Woods Hole, is published this
week in Nucleic Acids Research.
The discovery provides another jolt to the "central dogma" of
molecular biology, which states that genetic information is passed
faithfully from DNA to messenger RNA to the synthesis of proteins. In
2015, Rosenthal and colleagues discovered that squid "edit" their
messenger RNA instructions to an extraordinary degree -- orders of
magnitude more than humans do -- allowing them to fine-tune the type of
proteins that will be produced in the nervous system.
"But we thought all the RNA editing happened in in the nucleus, and
then the modified messenger RNAs are exported out to the cell," says
Rosenthal, senior author on the present study. "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." The team also showed that messenger
RNAs are edited in the nerve cell's axon at much higher rates than in
the nucleus.
In humans, axon dysfunction is associated with many neurological
disorders. Insights from the present study could accelerate the efforts
of biotech companies that seek to harness this natural RNA editing
process in humans for therapeutic benefit.
Scientists from Tel Aviv University and The University of California at Denver collaborated with MBL scientists on the study.
Previously, Rosenthal and colleagues showed that octopus and
cuttlefish also rely heavily on mRNA editing to diversify the proteins
they can produce in the nervous system. Together with squid, these
animals are known for strikingly sophisticated behaviors, relative to
other invertebrates.
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