Thursday, 21 February 2013

DIY RNA

Firstly, I’d like to apologise as I know this is not strictly marine microbiology. But it is a keen interest of mine and it was a toss-up between yet another post on bio-augmentation of oil degraders and this… And this won!

The question of “Where did we come from?” is a prominent one throughout history. Many see the answer as the Darwinian definition; that we came from Prehistoric apes. Others may think that LUCA, the Last Common Universal Ancestor, is the answer. However the study of abiogenesis has led to many real answers about the true origin of life through the primordial soup system as evidenced by the key research of Miller & Urey (1952). This experiment showed that basic amino acids and certain proteins will self-assemble under the correct conditions and thus this theory has been generally accepted.

However Cafferty et al (2013) have recently shown that much larger, much more complex molecules can self-assemble in water, and are very similar to RNA (which many think was a precursor to DNA). These molecules consist of two weakly interacting low-molecular-weight monomers (cyanuric acid and a modified triaminopyrimidine), which form non-covalent supramolecule through spontaneous assembly, completely absent of intermediates. This occurs through several, negative gibbs energy reactions which are documented in the paper.

Previously, no other attempt at this kind of research has been able to successfully dimerise RNA in water, unaided, without a polymer backbone.

Although I do not fully understand the biochemistry, from what I do understand Cafferty et al (2013) have managed to create proposed “proto-RNA” bases which spontaneously assemble into gene length (up to 18000 molecules) linear stacks. These molecules were visualised using TEM and Atomic Force Microscopy and characterised using NMR spectroscopy. Using these methods, large (>1µm) linear and branched fibrilliar structures were observed, which the authors claim are “the longest supramolecular polymers generated to date by untethered, monocyclic monomers in waters”.

Many questions about the origin of life can be answered with the conclusions drawn from this study, and further research is essential to see if this methodology can be incorporated into other areas of research, such as nanotechnology and the formation of synthetic nanowires.

REF: Brian J. Cafferty, Isaac Gállego, Michael C. Chen, Katherine I. Farley, Ramon Eritja, Nicholas V. Hud. Efficient Self-Assembly in Water of Long Noncovalent Polymers by Nucleobase AnaloguesJournal of the American Chemical Society, 2013; 135 (7) 2447
Accessed From: http://pubs.acs.org/doi/full/10.1021/ja312155v

3 comments:

  1. Hi Harri,

    Love this post, personally im an advocate of LUCA. have you read Richard Dawkins "Selfish Gene"? Dawkins gives an amazing account of the origin of life, which includes self replicating units of data!(I think that's how he put it). This paper is great as they repeated the results. The next step would be the formation of a polymer backbone to the bases, do you think this would be possible? Also how similar are the "proto-bases" to the bases we are used to in modern day life?

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  2. Hi Harri

    this is well interesting! You said that the reaction was driven spontaneously by ΔG < O, which would be in contrast to Miller and Urey's experiment, where 60000 Volts were run through the test tubes to provide energy for the reactions to occur and this irrealistic amount of energy supply was one of the main drawbacks of their hypothesis at that time. Did the authors mention how this big difference in energy requirement can be explained? Samples from the original Miller-Urey experiment were re-analysied in 2007 so I can't be a difference in methodology to detect and characterise the molecules...

    Also did Cafferty et al. indicate whether the initial mixture they used corresponded to any suggested original atmospheric or seawater compositions?

    Overall a great find though and will be interesting to see what the future of nanotechnology will make out of it!

    thanks

    Anna

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  3. Hey,

    Myles - Ah, I may not have made myself clear, of course I believe in LUCA too!! What I was trying to say is that when theories about where we came from are proposed, many feel that they are not enough and strive to go further back on the evolutionary timeline!
    Well the formation of a polymer backbone HAD to be possible otherwise we wouldn't be here! And indeed, the paper I reviewed was a e-publication ahead of print and the authors state that the next step in their research is to find the mechanism of formation of a backbone. I would like to imagine they are working on it right now!

    Anna - Yes, sorry I should have made that clear too! While Miller & Urey where able to justify their result by the explanation of a lightning bolt, this research is far far more valid. The authors state that the "interactions are weak and were created with the concept of a minimum hydrophobic surface area in mind". My personal grasp of this is that they added different substrates in a specific, designed order in order to overcome the Gibbs energy laws. In addition to this, at no point in the paper the authors say anything about what temperature or pressure the system is at... Hmmm...

    Harri

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