What’s all the fuss about DNA and RNA mods then? The last few years has seen an explosion of these things in all the top journals. It went from steady classics, the everyday methylated cytosine, to a whole plethora of weird and wonderful modifications. Nowadays, everything has a modified version with its own sequencing method and quirky novel function. Let’s take a look, shall we?

5-methylcytosine (5mC)

The bread and butter of DNA mods. The classic. The stable, reliable fella you know will always be around. Unlike Pluto, 5mC won’t be declared a fake. It’s here, it’s real, and it will be around forever. It’s the Big Mac of the DNA mods. Everyone knows 5mC.  5mC is kind of a big deal. It’s such a big deal that some people consider it to be the 5th DNA base. First discovered back in 1948 (old news), it’s famous for it’s association with gene repression. However, 5mC is no one trick pony: even today new functions are discovered for our steady, dependable friend. So, keep your eye on this one.

N6-methyladenosine (m6A)

m6A to RNA is what 5mC is to DNA. Everyone who is anyone working on RNA mods will know m6A. It’s been around a while. Seen its fair share of Nature and Science papers. m6A is the Rolling Stones of the mods world – been there, done that, it knows it’s awesome. Much like 5mC, there is more than meets the eye with this mod. Researchers are finding new roles for m6A all the time: from modulating sex determination to hematopoietic stem cell specification. m6A has its fingers in all the biological pies.

5-hydroxymethylcytosine (5hmC)

Just when you thought 5mC was stable, along came 5hmC. Everything I thought I knew is a lie! What is this weird new version of 5mC? It turns out that you can take 5mC and oxidize it to make something else. This something else is 5hmC. A once mystical new mod that is now a bit old hat. Even considered by some to be the 6th DNA base. Once considered an unstable intermediate in DNA demethylation (going from 5mC to unmodified C), 5hmC is now recognized to have powers beyond this. In some situations, it is stable. It has its own readers/binders. It even has its own epigenetic roles! What a time to be alive.

Pseudouridine (Ѱ)

Much like Prince in the early 90’s, Pseudouridine is often referred to only as a symbol. In this case Ѱ, the Greek symbol Psi. So, what’s so exciting about this guy that it gets a super stylish symbol for a name? It’s only one of the most abundant modifications found on RNA! You take an mRNA, there’s Pseudouridine. You take a tRNA, there’s Pseudouridine. Take an rRNA, yep that’s right, there’s Pseudouridine. You can’t get away from this guy. It’s all over RNAs no matter the species. But what is it doing? Well, this is something that researchers are still pursuing. Recent advancements in the methods available for detecting RNA mods means that there is no better time to be researching these things than right now!

5-formylcytosine (5fC) and 5-carboxymethylcytosine (5caC)

You know earlier when I was banging on about the wonders of 5mC oxidation? Well turns out it doesn’t stop at 5hmC. It keeps going. Not once, but twice. Enter 5fC and 5caC! The world has gone 5mC oxidized derivative crazy. Turns out getting from 5mC back round to unmodified C is a multistep process. Why are we only hearing about these guys now? You find 5fC and even more so 5caC at very low levels throughout the genome. Thanks to advances in mass spec we can now quantify these hidden modifications. It’s thought these two are just DNA demethylation intermediates. Put there only to be removed. But what if there is more to these guys than just the life of an intermediate? Only time and some mighty fine research will tell.

DNA and RNA mods are cool, exciting, and everyone’s talking about them. Don’t get FOMO (Fear Of Missing Out). Get mod researching. You could be the next scientist to discover a new modification. Or finally, uncover the amazing hidden function of that mysterious mod no one understands yet. There are hundreds of modifications out there. Plenty to go around. So, get out there and make that awesome science!

Photo by Katya Austin

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