"Split genes and RNA splicing"

Date:
1979
Reference:
PP/CRI/I/1/31
Catalogue details

Licence: In copyright

Credit: "Split genes and RNA splicing". Source: Wellcome Collection.

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    Reprint Series T TT |VTI- 20 April 1979, Volume 204, pp. 264-271 ■ a Split Genes and RNA Splicing Francis Crick In the last 2 years there has been a mini-revolution in molecular genetics. When I came to California, in September 1976,1 had no idea that a typical gene (/) might be split into several pieces and I doubt if anybody else had. By the time of the annual Cold Spring Harbor Sym posium, in the summer of 1977, it was clear that there was something very strange about the arrangement of the genes in several mammalian viruses, and for this reason it seemed highly likely that some chromosomal genes would al so be in several pieces. This has since been found to be the case. Even though the experimental evidence is still very 264 patchy, it is now universally accepted that a gene in a higher organism, coding for a protein, may have other base se quences interspersed within it. This article is not a historical account of the discovery. The earliest pub lications can be tracked down by con sulting the Cold Spring Harbor volume on chromatin (2). Nor does it attempt to be a comprehensive review, both be cause that would take up too much space and also because experimental results are coming in all the time. I present here an overall view of the present position, fluid though it is, together with some general ideas and a few remarks about future work. A brief but very imaginative article by Gilbert (3), on similar lines to this one, has already appeared. Similar ideas have been presented by Tonegawa et al. (4). The Basic Problem It is easiest to begin by considering an imaginary example. The upper part of Fig. 1 shows schematically a length of DNA which codes for a single messenger RNA (mRNA). The lower part shows the base sequences found in that mRNA. The relation between the two is indicated by the lines connecting them. The figure shows that in this case there are two fair ly long stretches of base sequence along the DNA of the gene which do not ap pear in the final mRNA. Such sequences are now known as intervening se quences. An alternative terminology, used by Gilbert and his colleagues (3,4) refers to the intervening sequences as introns; those base sequences on the DNA which do end up in the mRNA are referred to as exons since they are the ones which are expressed. At this stage, any terminology is likely to lead, before long, to difficulties and complications (5). In this article I use the intron-exon terminology, if only for want of a better one. What possible mechanisms are there which could have produced this result? There are at least four that immediately spring to mind: The author is Kieckhefer Research Professor at the Salk Institute, San Diego, California 92112. SCIENCE, VOL. 204, 20 APRIL 1979 0036-8075/79/0420-0264$02.00/0 Copyright © 1979 A AAS Summary. A number of genes in higher organisms and in their viruses appear to be split. That is, they have nonsense stretches of DNA interspersed within the sense DNA. The cell produces a full RNA transcript of this DNA, nonsense and all, and then appears to splice out the nonsense sequences before sending the RNA to the cyto plasm. In this article what is known about these intervening sequences and about the processing of the RNA is outlined. Also discussed is their possible use and how they might have arisen in evolution.