Nature review: Origin of 'RNA world'

OK this is cool. Really cool. But I suck at chemistry so I'm gonna keep it real simple...

It's a given that life somehow emerged at least once on this planet about 4-4.5 billion years ago. Understanding how this amazing event happened is a major challenge though. There are a multitude of theories out there but problems tend to arise in trying to reproduce the origin of life event in the lab. One theory is that prior to DNA and protein-based life there was an exclusively RNA-based world. Indeed, this theory is probably widely accepted as the most plausible, if not the only possible, scenario.

As I said, each theory has it's own problems, and the RNA-world theory is no different. The main difficulty is how to combine the three elements of an RNA molecule, i.e. the nucleobase, the ribose and the phosphate. In particular, attempts to join together the nucleobase and the ribose have always been met with failure, casting doubt on the likelihood of these molecules spontaneously combining in Earth's early atmosphere...

That is until now.

Researchers Powner et al (1) have published results in Nature showing that a nucleobase and a ribose can combine in plausible early Earth conditions. They achieved this by using a totally different approach to previous attempts. It had long been assumed that the nucleobase and the ribose must have first formed independently and then joined together in a secondary reaction (See FigA). Instead, Powner and colleagues have now shown that the combined nucleobase-ribose molecule can emerge from a precursor molecule, side-stepping the need for both to first form independently (FigB). Specifically, "activated pyrimidine ribonucleotides can be formed in a short sequence that bypasses free ribose and the nucleobases, and instead proceeds through arabinose amino-oxazoline and anhydronucleoside intermediates"


Figure taken from article by Jack Szostak (2)

So this work gives a plausible mechanism for the origin of the 'RNA world'. Pretty cool, isn't it?

Well yes, but I've saved the best part till last.....

The catalyst for this series of reactions that combine a nucleobase and a ribose is........wait for it......

Phosphate!!

That's right. The third component of RNA is needed for the precursor molecules to form the activated pyrimidine ribonucleotides. Phosphate controls several steps in the reaction. Specifically, it "controls three reactions in the earlier stages by acting as a general acid/base catalyst, a nucleophilic catalyst, a pH buffer and a chemical buffer". Following completion of it's job as a catalyst, phosphate is then incorporated into the molecule at a later stage, thus completing the RNA synthesis. The beauty of this system is incredible, and is described perfectly by Szostak:

Phosphate continues to have several essential roles in the remaining steps of Powner and colleagues' pathway, in one case causing depletion of an undesired by-product, and in another saving a critical intermediate from degradation. The penultimate reaction of the sequence, in which the phosphate is attached to the nucleoside, is another beautiful example of the influence of systems chemistry in this set of interlinked reactions. The phosphorylation is facilitated by the presence of urea; the urea comes from the phosphate-catalysed hydrolysis of a by-product from an earlier reaction in the sequence.

This work represents a major breakthrough in our understanding of how life might have emerged as it has provided an elegant mechanism for the spontaneous generation of RNA. As always, more research needs to be done, but we now have an exciting new perspective on an age-old problem.


(1) Powner et al. Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions. Nature 459, 239-242 (14 May 2009)

(2) Jack W. Szostak. Origins of life: Systems chemistry on early Earth. Nature 459, 171-172 (14 May 2009)