"On protein synthesis"

Date:
1958
Reference:
PP/CRI/I/1/16
Catalogue details

Licence: In copyright

Credit: "On protein synthesis". Source: Wellcome Collection.

    9/14
    of the composition of protein molecules and the simplicity of the nucleic acids. Work is actively proceeding in several laboratories, including our own, in an attempt to provide more direct evidence for this hypothesis. The Central Dogma This states that once ' information ' has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is im possible. Information means here the precise determination of sequence, either of bases in the nucleic acid or of amino acid residues in the protein. This is by no means universally held—Sir Macfarlane Burnet, for example, does not subscribe to it—but many workers now think along these lines. As far as I know it has not been explicitly stated before. Some ideas on cytoplasmic protein synthesis From our assumptions it follows that there must be an RNA template in the cytoplasm. The obvious place to locate this is in the microsomal particles, because their uniformity of size suggests that they have a regular structure. It also follows that the synthesis of at least some of the micro somal RNA must be under the control of the DNA of the nucleus. This is because the amino acid sequence of the human haemoglobins, for example, is controlled at least in part by a Mendelian gene, and because spermatozoa contain no RNA. Therefore, granted our hypotheses, the information must be carried by DNA. What can we guess about the structure of the microsomal particle? On our assumptions the protein component of the particles can have no significant role in determining the amino acid sequence of the proteins which the particles are producing. We therefore assume that their main function is a structural one, though the possibility of some enzyme activity is not excluded. The simplest model then becomes one in which each particle is made of the same protein, or proteins, as every other one in the cell, and has the same basic arrangement of the RNA, but that different particles have, in general, different base-sequences in their RNA, and therefore produce different proteins. This is exactly the type of structure found in tobacco mosaic virus, where the interaction between RNA and protein does not depend upon the sequence of bases of the RNA (Hart & Smith, 1956). In addition Watson and I have suggested (Crick & Watson, 1956), by analogy with the spherical viruses, that the protein of microsomal particles is probably made of many identical sub-units arranged with cubic symmetry. On this oversimplified picture, therefore, the microsomal particles in a cell are all the same (except for the base-sequence of their RNA) and are metabolically rather inert. The RNA forms the template and the protein supports and protects the RNA. This idea is in sharp contrast to what one would naturally assume at first glance, namely that the protein of the microsomal particles consists entirely of protein being synthesized. The surmise that most of the protein is structural was derived from considerations about the structure of virus particles and about coding; it was independent of the direct experimental evidence of Zamecnik and his colleagues that only a small fraction of the protein turns over rapidly, so that this agreement between theory and experiment is significant, as far as it goes. It is obviously of the first importance to know how the RNA of the particles is arranged. It is a natural deduction from the Sequence Hypo thesis that the RNA backbone will follow as far as possible a spatially regular path, in this case a helix, essentially because the fundamental operation of making the peptide link is always the same, and we therefore expect any template to be spatially regular. Although we do not yet know the structure of isolated RNA (which may be an artifact) we do know that a pair of RNA-like molecules can under some circumstances form a double-helical structure, somewhat similar to DNA, because Rich & Davies (1956) have shown that when the two polyribotides, polyadenylic acid and polyuridylic acid (which have the same backbone as RNA) are mixed together they wind round one another to form a double helix, presumably with their bases paired. It would not be surprising, therefore, if the RNA backbone took up a helical configura tion similar to that found for DNA. This suggestion is in contrast to the idea that the RNA and protein interact in a complicated, irregular way to form a 'nucleoprotein'. As far as I know there is at the moment no direct experimental evidence to decide between these two points of view. However, even if it turns out that the RNA is (mainly) helical and that the structural protein is made of sub-units arranged with cubic symmetry it is not at all obvious how the two could fit together. In abstract terms the problem is how to arrange a long fibrous object inside a regular poly hedron. It is for this reason that the structure of the spherical viruses is of great interest in this context, since we suspect that the same situation occurs there; moreover they are at the moment more amenable to experimental attack. A possible arrangement, for example, is one in which the axes of the RNA helices run radially and clustered in groups of five, though it is always possible that the arrangement of the RNA is irregular.