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RNA DNA RNA PROTEIN ?What is Life? Charles Jencks Indeed it is a question, a perplexing one that has exercised humanity as long as we have been speculating about the fundamental issues. We do not have the answer – and are not sure if there is a single one – but we have discovered some of the necessary ingredients of life and that fact is worth noting in a garden. Between the two question-marks above we do know some of the middle. It is a victory won after a long period of investigation, and celebrated here for the first time in public sculpture. If you descend down a main pathway at Dublin’s Botanic Garden towards the waterway and lily pond that lies at its heart, you come upon a landform emerging from behind some trees. Curving over its back are twisting ribbons that rise up in breaking waves. These culminate in a silver-coloured sculpture of curling aluminum out of which springs a single coil, an enigmatic shape – the protein that builds you. But beyond this mysterious coil is a recognizable structure that dominates the ensemble, the well-known form of DNA. This double helix, the high point of the spiral route, is the first great clue to the recipe for life, elucidated by Watson, Crick, Wilkins and Franklin in 1953. As you walk towards it you can read phrases cut into the metal. These describe what is recently understood as a key agent, RNA, the molecule with many great abilities. It catalyzes and replicates, possibly even itself. Mostly likely it preceded DNA and, as “The First Multitasker,” it interprets, regulates and repairs life. Its twisting forms are as numerous as its known functions. Several RNAs dance over the crest of the wave, for instance the Hammerhead form that is blown up in size, many millions of times. No one fully understands the multiplicity of these molecules, which explains the question- mark of the path. But what we do know is that the multifunctional molecule of RNA is essential to life, and probably the major vehicle in early evolution. The ascending movement and the words imply there are a few more answers, and create a rising expectation. Waves become bigger, the phrases longer, the ascent steeper, the culmination clearer, suggesting a timeline from the initial question posed by Darwin – and cut into the first ribbon – did life start in “some warm little pond?” Were water and heat some of the preconditions? The search of many generations is itself a dramatic time-line. The ribbons and RNA- waves rise up as an evolutionary sequence, yet on closer inspection they reveal that not only are there stories of progressive change in Acknowledgements Aluminum sculpture: Artist Charles Jencks; with advice from the molecular biologist, John Atkins; fabricator, John Gibson. The text of the talk by John Atkins is available on request to [email protected] Brochure Design: Mary Heapes, Department of Biochemistry, UCC. a line, but they are punctuated by setbacks and regressions. These dead ends here reach down into the ground and, incidentally, provide lateral support to the structure (and narrative). Two steps forward, one or two back. Evolution is a hill to climb with tragic as well as positive consequences. Sometimes RNA is a viral threat – sometimes it suppresses a virus. At the head of the path the double helix is reached, and its harmonic shapes and symmetries remind us that beauty is a natural product of life and chemistry, not just a human projection or a matter of taste. At certain moments when it opens up DNA can be very elegant, and I have tried to capture these sculptural instants with its flying, structural armature. These parallel spirals do encode information it is true, but utility is neither a guarantee of elegance nor its opposite. In fact, DNA in different states is both beautiful and, when supercoiled, ugly like a mess of spaghetti. Aesthetic value is as real and basic as morality, and any cosmic code. At this point of the path three seats are visible on which ideas are spelt out in words of black: whatever life is it is a series of messages, as well as physical embodiment. Thus the large mound shows a print-out of coded information that comes out of the biggest RNA sculpture here. This is the famous Ribosome, where the spaghetti is the most intricate because the machinery must perform complex work. It must synthesize the protein, which can be seen coming out of the top. This looks like a little ‘corkscrew,’ but perhaps it is the biggest product, the thing that makes us. Such codes keep life on message – CCG, UUA, etc which are marked – and then the seat elements highlight the words Frame Shift, as they do a little dance. This surprising shift is marked strongly because it gives RNA some of its great versatility, something to contemplate as you sit down on the words. Closer in the foreground, and to the right, is the LUCA seat, the ‘last universal common ancestor’ that we presume is the start to the cellular evolutionary sequence, while just beyond this white inscription is Circular RNA, another seat that indicates one more powerful function recently discovered about this Protean molecule. According to some metaphors of scientists it can ‘block the blockers’ or, ‘like a sponge,’ soak up some undesirable messages creating Parkinson’s disease and cancer. If it is as powerful as we surmise, then as Editor in Chief it corrects the mistakes introduced by sub-editors. But whatever the correct metaphor, Circular RNA typifies the amazing variety of important, new functions being discovered today. The symbolism does not end with seats. Two more elements, metal ribbons, signal across the open space to each other. One is a positive arrow, the other its negative receptacle. The first says loud and clear in dark black “RNA controls“, while the other, the right arm of the double helix, rises up to accept the message: “DNA expression.” That message, shooting across open space, conveys a powerful truth understood in the last few years. What are the implications, why all the expressive signs? It turns out that RNA is a part of the epigenetic revolution underway for thirty years, the emerging knowledge of how we can influence and change our genomic inheritance through modifying our lifestyle, and with more direct genetic intervention. In mice and men radical changes in diet – starvation and over-indulgence – can under certain conditions affect gene expression two generations hence. Also as Adrian Bird, an authority on epigenetics, contends ‘we know that conditions during pregnancy, including maternal diet, have long-term health consequences for the offspring right into adult life,’ (New Scientist, 5 January, 2013). As for direct attack, he says, ‘that drugs targeting epigenetic processes can be effective anti-cancer agents…epigenetic disturbances are the Achilles heel of certain cancers’ [when the dose of an intervention is made at less than toxic level]. Genes can be active (or expressed) and turned off (or silenced) and this regulation is carried out by The First Multitasker, RNA. It is true this twisting molecule can be sometimes ugly, complex and multiform. Nevertheless, because it can respond to many lifestyle diseases, we may soon respect (perhaps even love) our RNA. The epigenetic revolution reveals that the potential of a gene to be expressed is able to pass along with the germ line. In other words, the way we live our lives may influence the potential of some genes we pass to our offspring, and that gives us a degree of self-determination, and responsibility for future generations. The hope is that further genetic understanding, and intervention, will increase our control still more. Genetic determinism is a two-way street, a human freedom honored here in the dance of eruptive molecules. ?What is Life? remains a question-mark at both ends of the journey, but in the last few years we have discovered basic truths about life, and they will continue into the future.
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