In their natural habitats, octopus and squid are subject to wide temperature fluctuations throughout the year. However, as cold-blooded animals, they cannot regulate their body temperature themselves. How do they protect their powerful brains anyway? Two studies now show that octopus and squid change their mRNA in different ways depending on the ambient temperature. This results in modified proteins that guarantee the optimal functioning of the brain at cold or warm temperatures.
The blueprints for proteins are stored in DNA. So that these blueprints can be implemented, the DNA is first translated into so-called messenger RNA (mRNA) when it is read - the blueprint on the basis of which the proteins are then formed. In order to increase the diversity of the available proteins, the mRNA in humans and animals is subsequently edited in many cell types. Individual letters of the code are deleted, inserted or changed. This RNA editing can be used to create different proteins from the same DNA template, depending on the cell type. In humans, editing affects about three percent of genes.
Kraken recoding
Two research teams have now independently demonstrated that cephalopods such as octopuses and squids use RNA editing to a far greater extent. "RNA recoding gives organisms the ability to express a variety of proteins when and where they want," says Joshua Rosenthal of the Marine Biological Laboratory in Woods Hole, Massachusetts. "In cephalopods, recoding is predominantly for proteins important to nervous system function, raising the question of whether they use this to adapt to changes in their physical environment."
In order to clarify this question, Rosenthal and first author Matthew Birk and their team first carried out experiments with wild-caught adult two-spotted octopuses (Octopus bimaculoides). These are small, yellowish-brown octopuses that have two shimmering blue dummy eyes under their real eyes. These octopuses live off the coasts of California and Mexico, and their genomes have already been sequenced. For several weeks, the researchers kept the octopuses in either 22 degrees warm or 13 degrees cold water and then investigated how the DNA is converted into RNA and proteins. They focused on around 60,000 previously identified locations in the genome where editing can occur.
Adaptation to different temperatures
It showed: "Temperature-sensitive editing occurred at about a third of these locations - at over 20,000 individual sections. So it's not a phenomenon that occurs here or there, but a global phenomenon," says co-author Eli Eisenberg of Tel-Aviv University. "However, this does not happen to the same extent: proteins that are edited tend to be neuronal proteins, and almost all sites that are temperature-sensitive are edited more strongly in the cold." Using the example of the two proteins kinesin and synaptotagmin, which play an important role play in the nervous system, the researchers also investigated how mRNA editing affects the structure and function of the proteins. They found that the recoding actually causes structural changes in the proteins and that the proteins produced by cold or heat were adapted to the corresponding temperature range.
But how quickly is the change in protein production possible? "We had no idea if it would take weeks or hours," says Birk. Therefore, in another experiment, the researchers placed young octopuses, only the size of a thumbnail, in cold water of 14 degrees and heated it by 0.5 degrees per hour to 24 degrees – and vice versa. Immediately before and after the temperature change and four days later, they examined the extent of RNA editing. "We were able to see significant changes in less than a day, and within four days they were back to where they were after a month," Birk reports.
Widespread mechanism?
Additional results suggest that the mechanism is widespread in cephalopods. On the one hand, Birk and his team were able to demonstrate temperature-dependent RNA editing in wild California two-spotted octopuses at different times of the year, as well as in individuals of a closely related species. On the other hand, an independent research team led by Kavita Rangan from the Howard Hughes Medical Institute in Maryland found similar ones Results obtained on opal squid (Doryteuthis opalescens). "Our work suggests that squid can adapt their proteome, i.e. the entirety of their proteins, on the fly in response to changes in sea temperature," says Rangang's colleague Samara Reck-Peterson. "One can speculate that this ability allows these cold-blooded sea creatures to survive in a wide range of sea temperatures."
Since several recodings took place in proteins that also occur in humans, the discovery could also be of medical interest. "The recoding sites of cephalopods can possibly point us to residues with functional importance in highly conserved proteins," says Rangan. "This has far-reaching implications for our understanding of basic protein functions and for the development of proteins with specific functions. Cephalopods may be able to show us where to look and what changes to make.”
Sources: Matthew Birk (Marine Biological Laboratory, Woods Hole, Massachusetts) et al., Cell, doi: 10.1016/j.cell.2023.05.004; Kavita Rangan (Howard Hughes Medical Institute, Chevy Chase, Maryland) et al., Cell, doi: 10.1016/j.cell.2023.04.032