Systems Chemistry in the Prebiotic Synthesis of RNA

It is though that during the origin of life on Earth there was a phase when the nucleic acid RNA served the dual roles of information storage and catalysis. The 'RNA world hypothesis' is strongly supported by much recent biological work, but until our recent EPSRC funded work, there had been little by way of chemical explanation as to how RNA might have been generated prebiotically on the early Earth. To quote from a New York Times article written about our work earlier this year: 'For more than 20 years researchers have been working on this problem. The building blocks of RNA, known as nucleotides, each consist of a chemical base, a sugar molecule called ribose and a phosphate group. Chemists quickly found plausible natural ways for each of these constituents to form from natural chemicals. But there was no natural way for them all to join together. The spontaneous appearance of such nucleotides on the primitive earth would have been a near miracle, two leading researchers, Gerald Joyce and Leslie Orgel, wrote in 1999. Others were so despairing that they believed some other molecule must have preceded RNA and started looking for a pre-RNA world.The miracle seems now to have been explained. In the article in Nature, Dr. Sutherland and his colleagues Matthew W. Powner and Batrice Gerland report that they have taken the same starting chemicals used by others but have caused them to react in a different order and in different combinations than in previous experiments. they discovered their recipe, which is far from intuitive, after 10 years of working through every possible combination of starting chemicals. Instead of making the starting chemicals form a sugar and a base, they mixed them in a different order, in which the chemicals naturally formed a compound that is half-sugar and half-base. When another half-sugar and half-base are added, the RNA nucleotide called ribocytidine phosphate emerges. A second nucleotide is created if ultraviolet light is shined on the mixture.'So far so good, but quite a bit remains to be done if RNA itself is to be made, and the current proposal seeks funds to finish the job. In particular, we want to:i) find a route to activated purine nucleotides - we think we can do this from a by-product of the pyrimidine nucleotide synthesisii) sort out the chirality issue (certain molecules exist in left and right handed forms, and RNA is a polymer of right handed nucleotides) - we think we can do this using a crystallisation 'trick' followed by a phosphate-catalysed reactioniii) find a route to glyceraldehyde which is a key intermediate in the synthesis, but which is not considered to have been a prebiotic feedstock moleculeiv) optimise conditions for stringing the activated nucleotides together to generate RNA

Who will benefit from this research, and how? i) Those members of society interested in the origin of life, through intellectual satisfaction. ii) Academic and industrial chemists, through (unpredictable) scientific and technological 'spin outs'. In support of i), our previous EPSRC work in this area has recently hit the headlines worldwide eg. 'Chemist Shows How RNA Can Be the Starting Point for Life', The New York Times, May 13 2009. 'RNA world easier to make', Nature News, May 13 2009. 'Found: the origin of life. Scientists solve the mystery of how the Earth was transformed' The Independent, 14 May 2009. 'Molecule of life emerges from laboratory slime' New Scientist, 13 May 2009. 'Sur les traces de l'origine de la vie' Le Figaro, 15 May 2009. 'L'origine della vita ricreata in laboratorio' Corriere Della Sela, 14 May 2009. 'Nieuw bewijs voor de theorie dat het leven uit RNA is voortgekomen' NRC Handelsblad, 16 May 2009. 'Scientists closer to finding origins of life' The New Zealand Herald, 15 May 2009. It is more difficult to provide support for ii), but experience indicates that it happens often. What will be done to ensure they benefit from this research? We will continue to publish our results in leading journals, and publicize it through written and audiovisual media.