Lewis Wolpert: 'There is now evidence that RNA - a relation of DNA - is involved in diseases ranging from cancer to schizophrenia'

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The Independent Online

DNA, Deoxyribonucleic Acid, the material of genes, is doing very well. Last year there were worldwide celebrations for the 50th year since Watson and Crick discovered its double-helical structure, and so understood how it replicated. It is at the core of life, for in all cells it is DNA alone that replicates.

DNA, Deoxyribonucleic Acid, the material of genes, is doing very well. Last year there were worldwide celebrations for the 50th year since Watson and Crick discovered its double-helical structure, and so understood how it replicated. It is at the core of life, for in all cells it is DNA alone that replicates.

DNA is everywhere in the news, with all the so-called ethical problems of genetics, and with human DNA and that of other animals having been sequenced. But what about its near relation, RNA, ribonucleic acid? It must feel very neglected, even jealous, for it too plays a key role in cellular life - and a new and exciting role has just been revealed.

DNA carries the code for proteins. But in 1960, how the information from the DNA was used to make proteins was not known. It was thought that little particles containing RNA, ribosomes, carried the message from the DNA for making proteins. But there was evidence that this could not be true, as no new ribosomes were made when new proteins had to be made.

There was a meeting on Good Friday in 1960 in Sydney Brenner's rooms at King's College in Cambridge to discuss the problem. It was at this meeting that, as Brenner has said "the penny dropped" when he and Crick suddenly realised that there must be another RNA carrying the message.

He then arranged with the French molecular biologist François Jacob to try to identify the messenger RNA while they were both in California, where they had been invited for quite different reasons. They worked very hard but things were going wrong with their experiments. They went down to the beach to rest and reflect, as time was running out. Reflection led Brenner to suddenly leap up and shout, "It's the magnesium". They were not adding enough. Back they went, and it worked, and they discovered messenger RNA. Both have Nobel Prizes, but this should have been another one.

Messenger RNA carries the code for making proteins from the DNA to the ribosome. The messenger RNA is synthesized on the DNA gene for the protein, which acts as a template. It then leaves the DNA and binds to a ribosome and in a quite complex process the code is then translated into the sequence of amino acids that make up a particular protein.

It is, of course, proteins that are the wizards of the cell, as they determine the form and function of the cell; for example, in muscle it is special proteins that enable the muscle to contract. Genes, by comparison, are rather boring and passive, but turning them on allows messenger RNA to be made, and thus the relevant proteins. Enormous efforts are devoted to studying when and where genes are turned on during embryonic development, as well as in situations such as cancer where the wrong genes are turned on.

A peculiar feature of human DNA and related animals is that most - almost 98 per cent - of the DNA does not code for proteins, and so it has been a puzzle as to what it does. Some of it is for controlling when and where a gene is turned on, as special proteins bind to these control regions and determine the on/off status of a gene. But the new view is that much of the DNA codes for special non-coding RNAs, which act as regulatory signals. These non-coding RNAs can act by binding to messenger RNAs and effectively making them inactive, and they can also act as regulators of gene activity.

Much of the DNA is thus not for protein-coding but for these regulatory non-coding RNAs. As many as 20 per cent of all human genes can effectively be silenced by these non-coding RNAs. There is also evidence that these RNAs are involved in human diseases ranging from cancer to schizophrenia. RNA has now an elevated status. The level of complexity in the cell was known to be high before this discovery, but now goes even higher.

It is a major problem to determine and understand the interactions that may occur between thousands of different molecules. But the RNA community of scientists is very excited.

Lewis Wolpert is Professor of Biology as Applied to Medicine at University College, London

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