Octopus Can Edit Their RNA – Here’s How

Ever wonder why people label octopuses as “aliens“? It’s not because they hitched a ride on a meteor from outer space. Nope, these eight-armed geniuses earned their intergalactic reputation by doing something no other Earthling does quite like them: rewriting their own genetic instructions. RNA editing is a fascinating biological process employed by cephalopods (octopus, squid, and cuttlefish) to modify their genetic blueprint in ways that set them apart from nearly every other living creature. Pretty wild, right? 🐙✨

What is RNA Editing?

Time for a quick crash course in biology! So what exactly is this process? First, let’s start off with the basic unit of life– cells. All living organisms are made of one or multiple cells. These cells run the living world- containing the tools to provide the body with structure, take in nutrients from food, convert nutrients to energy, and also contain the body’s genetic blueprint material– DNA (Deoxyribonucleic acid). The genetic information in DNA is stored as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T).  From your middle school text book you probably remember this double helix structure with its bases paired up: A-T, G-C. Sequences of these base pairs is what makes up a gene which provides instructions for making essential proteins that do most of the work in our bodies. How this is done is through DNA transcription and translation. DNA is “unzipped” by a special protein called an enzyme and a copy is made. This single stranded copy of DNA is called RNA (you probably guessed it- Ribonucleic acid). The bases in the RNA are the same except thymine (T) is replaced with uracil (U). Bases are read in threes (known as a codon) by a protein makin’ machine known as a ribosome. This is the translation part where RNA is then made into a chain of amino acids aka a protein! Imagine DNA as your blueprint and RNA as the step-by-step guide for turning that blueprint into reality, producing the proteins needed to keep our body functioning! 

How RNA Editing Differs from DNA Mutation

Now that we’ve covered the basics DNA-> RNA->Protein, let’s get to the cool stuff– RNA editing. Humans and most other living organisms evolve and change through random DNA mutation. Coleoid cephalopods; however, are evolving through random DNA mutation to a lesser extent. Scientists discovered this when they analyzed a gene responsible for helping an organism adapt to different temperatures from a tropical octopus, Octopus vulgaris, and an Antarctic octopus, Pareledone sp. To their surprise, this gene was almost identical when comparing tropical versus Antarctic octopus species. One would think this gene has evolved over time to compensate for these temperature differences; however, this wasn’t the case! Also, this same gene was almost identical in a squid species, Loligo pealeii. So, the question remained, how are these octopuses acclimating to these two very different environments with the exact same blueprint or same DNA code?

A Surprising Discovery in Octopus Genes

The answer was in their RNA. Instead of changing the blueprint (DNA), like most animals do, octopuses are editing the step-by-step guide. The specific type of RNA editing cephalopods are using is A-to-I editing (remember Basics of Biology–  the RNA base pairs!). This happens when an enzyme called ADAR (adenosine deaminase acting on RNA, portrayed above as a giant pacific octopus), converts the RNA base A to an I (Inosine, read as a G-guansine during translation). Remember, these bases are in groups of 3, a codon, that codes for a different amino acid, combining multiple amino acids to make a protein. Changing only one RNA base (A, G, T, U) can result in an entirely new amino acid, and subsequently could alter a protein.

Is Human RNA editing Similar to Cephalopods?

Does this make them aliens? – maybe not. Cephalopods aren’t the only ones to do RNA editing. We humans do it as well. Researchers have identified thousands of editing sites in humans, but most exist in regions that don’t produce proteins and instead function to prevent unwanted immune responses. These sites are just patching up the RNA so nothing funky happens to us. Like fixing a mistake before you suffer the consequences. Sites that change one amino acid to another rarely happens in humans. However, the number of identified A-to-I editing sites in coleoid cephalopods is upwards of 600,000! These sites change amino acids and affect proteins. Not just house cleaning and mistake fixing, but renovations. Some of these renovations even pass on to their offspring. Currently, this is several magnitudes higher than any other organisms scientists have studied. 

RNA Editing and the Octopus Brain

A lot of this RNA editing is changing the function of proteins in the octopus’s brain. It happens in other tissues as well, but not to the same extent. Slight variations, such as increasing the rate that neurons are firing or the rate nerve cells are communicating and passing along an important message. This lends its hand (or arm) to quick decision-making and cepahlopod’s rapid adaptive camouflage, which is under direct control of their neurons reacting and communicating. Protein changes identified thus far are also affected by temperature, specifically cold water, and the protein variations stick around, giving the animals options to “choose” which variation best fits their circumstance. So octopus, which is it- Antarctica or the Tropics? 

Adapting to the Environment: Short-Term vs Long-Term Changes

The coolest discovery scientists have found (so far) is that the modified protein is implemented within 24 hours. Meaning this is a tool cephalopods are using for short-term environmental acclimation. Not just species in two different parts of the world, but locally, from upwelling currents to seasonal change. So in cephalopods, RNA editing is more beneficial than mutations. This means that their DNA isn’t changing much. They are making less long-term changes to acclimate to their environment in the short-term. It’s a clear give and take, but was it the right move? Well when we look at the history of cephalopods, they’ve survived 5 mass extinctions. They’ve been on this planet longer than trees have, and for a while they ruled the oceans.

Protecting our Oceans = More Insights from RNA Editing

RNA editing in cephalopods is a fairly recent field, so we have far more questions than answers. I hope I’ve given you a new topic to ponder about and a little glimpse at how cool life on this planet can be. We are just now really beginning to really understand cephalopods, and as more research continues to develop, we’re given an idea of how life can evolve in completely different ways than we’ve imagined. We also are able to use this knowledge to benefit humans, like with the development of non-addictive pain treatment based on RNA editing research. This is why it’s so important to protect the oceans while we have them, to protect the knowledge we will one day discover.

References:

Birk, Matthew A., Noa Liscovitch-Brauer, Matthew J. Dominguez, Sean McNeme, Yang Yue, J. Damon Hoff, Itamar Twersky, et al. “Temperature-Dependent RNA Editing in Octopus Extensively Recodes the Neural Proteome.” Cell 186, no. 12 (June 2023): 2544-2555.e13. https://doi.org/10.1016/j.cell.2023.05.004.

Garrett, Sandra, and Joshua J. C. Rosenthal. “RNA Editing Underlies Temperature Adaptation in K ⁺ Channels from Polar Octopuses.” Science 335, no. 6070 (February 17, 2012): 848–51. https://doi.org/10.1126/science.1212795.