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My attraction to darkness and how that led to RNA translation


How I got into RNA translation
Gerald Edelman Scientist
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Let me say that if someone asked me ten years ago would I be working on translation, which is the process of reading out the sequence of messenger RNA to make protein sequence – finally to yield functional protein products – I would say they're out of their mind. But it turned out that that's the way it was. And it might be worthwhile saying how I got into it because it is by error.

One day I said to my friend and colleague Bruce Cunningham, 'You know the ribosome', which is that structure which is involved in actually reading the sequence of message, and it's quite an intricate sort of super-macromolecule made of sub-units, quite definite with both so-called ribosomal RNA as its component as well as protein. I said, 'You know these ribosomal proteins must be very critical – we should make antibodies against every one and see what that means for translation.' And he started to do that, at which point X-ray studies appeared from other laboratories, particularly that of Steitz, and those X-ray studies indicated that, by golly, it wasn't really the protein at all although the protein has an unknown function; it was the actual ribosomal RNA that was involved in the translation process. So to make it clear, let me say what translation is and involves.

As you know, the sequence of the DNA in the gene, in the genome, in the nucleus, is read out by a process called transcription, and there are several intermediary steps when you make the RNA out of that that I won't mention. But eventually you get a so-called message. And that message contains essentially three types of components. One is called the 5 prime untranslated region – that's right at the head-end – and at the tail end is the 3 prime untranslated region, and in the middle is the coding sequence. And what really is supposed to have been happening in the field is that in eukaryotes – that is organisms with true nuclei, not just bacteria – the... the message has something called a cap, which is a modified guanosyl residue. And then what happens is you're supposed to bind at the cap the ribosomal small sub-unit and then it dances along in something called scanning until it reaches the first start-code on UAG that really counts and then you're off to the races, reading the code and inserting amino acid after amino acid according to the code. Well, that's the dogma.

It turns out however that, once I learned that we were wrong about assuming the role of the proteins, we got sort of interested and, in the course of doing that, we found something quite startling which we still don't quite understand, and that is, if you look at the actual sequence of the ribosomal RNA in specific portions, you find that sequence represented right inside the message, or inside the 5 prime or 3 prime UTR of various messages that don't seem to be related. They're sort of like sequence ladders and they're very homologous or complementary. But that I mean they're either the same sequences you find in this 18 SRNA of the ribosome, which isn't a coding structure but is involved in translation, or they're complementary to it in the sense of Watson Crick, they have the opposite kind of reading for the code. And we still are nonplussed. We don't have any idea of how that happened.

US biologist Gerald Edelman (1929-2014) successfully constructed a precise model of an antibody, a protein used by the body to neutralise harmful bacteria or viruses and it was this work that won him the Nobel Prize in Physiology or Medicine in 1972 jointly with Rodney R Porter. He then turned his attention to neuroscience, focusing on neural Darwinism, an influential theory of brain function.

Listeners: Ralph J. Greenspan

Dr. Greenspan has worked on the genetic and neurobiological basis of behavior in fruit flies (Drosophila melanogaster) almost since the inception of the field, studying with one of its founders, Jeffery Hall, at Brandeis University in Massachusetts, where he received his Ph.D. in biology in 1979. He subsequently taught and conducted research at Princeton University and New York University where he ran the W.M. Keck Laboratory of Molecular Neurobiology, relocating to San Diego in 1997 to become a Senior Fellow in Experimental Neurobiology at The Neurosciences Institute. Dr. Greenspan’s research accomplishments include studies of physiological and behavioral consequences of mutations in a neurotransmitter system affecting one of the brain's principal chemical signals, studies making highly localized genetic alterations in the nervous system to alter behavior, molecular identification of genes causing naturally occurring variation in behavior, and the demonstration that the fly has sleep-like and attention-like behavior similar to that of mammals. Dr. Greenspan has been awarded fellowships from the Helen Hay Whitney Foundation, the Searle Scholars Program, the McKnight Foundation, the Sloan Foundation and the Klingenstein Foundation. In addition to authoring research papers in journals such as "Science", "Nature", "Cell", "Neuron", and "Current Biology", he is also author of an article on the subject of genes and behavior for "Scientific American" and several books, including "Genetic Neurobiology" with Jeffrey Hall and William Harris, "Flexibility and Constraint in Behavioral Systems" with C.P. Kyriacou, and "Fly Pushing: The Theory and Practice of Drosophila Genetics", which has become a standard work in all fruit fly laboratories.

Tags: Bruce Cunningham, Watson Crick

Duration: 3 minutes, 40 seconds

Date story recorded: July 2005

Date story went live: 24 January 2008