In his letter Khorana reported progress in his ongoing effort to synthesize in the laboratory a gene that codes for the transfer
RNA of the amino acid tyrosine. In particular, he described work on the synthesis of the promoter sequence, a segment of
DNA, usually located before a gene coding region in the base sequence, which acts as a controlling element in the expression
of that gene, for example by regulating the beginning and the speed of transcription from DNA to RNA. Khorana also discussed
the terminator sequence, which signals the end of the polypeptide chain in protein synthesis. He detailed the structure of
the promoter and terminator sequences in schematic drawings attached to his letter.
Number of Image Pages:
6 (368,720 Bytes)
1974-05-22 (May 22, 1974)
Khorana, H. Gobind
Original Repository: Wellcome Library for the History and Understanding of Medicine. Francis Harry Compton Crick Papers
Thanks for your letter. I was glad that you were interested in the promoter sequence. I shall briefly bring you up-to-date
with the different aspects of the work on the tyr tRNA gene and my other research interest as well.
The enclosed sheets essentially summarize the status of the work.
(1) Synthesis: The DNA corresponding to the transcribed part of the gene (Smith-Altman precursor) has been synthesized.
The focus is now on the synthesis of the terminator and promoter regions.
(2) The promoter sequence (sheets 2 and 3) looks very beautiful to me. It could hardly be without significance. Transition
from the "regular" DNA to the looped out form could be aided by the enzyme without loss of the essential recognition
features and strand selection and site selection could both be accomplished in the process??
(3) The terminator sequence is on sheets 4 and 5. This too is interesting. Whatever the postulates at this stage, I am discontinuing
sequencing just now and, instead, we are setting up precise systems (containing the known sequences for the signals and the
adjacent parts) for studies of initiation and termination of transcription. After all, we have to prove the significance
and lengths of sequences in the start and stop regions by actually carrying out transcription. If necessary, we shall go
back to do more sequencing.
The ultimate goal is still to have a gene which is functional in in vitro transcription by virtue of its own signals. This
should then provide a powerful approach to systematic alterations of the structural gene. Also, I would like to add our synthetic
promoter and terminator to ends of "indifferent" DNA's to really prove what part does what.
Although this work takes up much of my effort just now, I hope that I shall be done with all this in the next year or so.
In the last couple of years I have also become very deeply interested in the chemistry of membranes and have had a small group
working in this field. Last fall I spent some time with Racker and his group at Cornell and this was most stimulating. I
am still running a minor collaboration with him on reconstitution of membrane functions. At least this much I have definitely
concluded that this sort of work is a reasonable starting point with my limitations and, especially, my deficient biological
I enjoyed your article in the 21st Anniversary issue of the DNA structure. If you have other writings in press, I would love
to receive copies.
I hope all goes well in Cambridge researchwise and with your family. My warm regards to them.
With best wishes,
H. Gobind Khorana
P.S. If you had any comments or thoughts on my above DNA work, I should of course be very happy to hear about them.
[DIAGRAM="Synthetic Tyrosine tRNA Gene"]
[DIAGRAM="Sequence in the Promoter Region of the tRNA Gene (Symmetry and Secondary Structure)"]
[DIAGRAM="Possible Secondary Structure of the Promoter Region"]
[DIAGRAM="Possible Secondary Structure of Terminator Region"]