ANTISENSE DISCUSSION

Stephen R. Lasky Stephen_Lasky at brown.edu
Fri Feb 9 08:59:31 EST 1996


Paul:  I'm confused enough, but I think that we've been through the
convention discussion before.  I was unable to find any reference that
used the terms sense and anti-sense in the orientation cited below before
1987.  Before that time the convention was the opposite:  The sense strand
of the DNA hybridzed to the mRNA.  The definitions changed in thelate 80's
or early 90's.  

On anti-sense proteins, if you go back to about 1986 and 1987 a researcher
named Blalock (I think) proposed that antibodies made against a protein
transcribed and translated from the opposite strand of the region of a
gene that codes for the ligand binding site in a receptor molecule would
recognize the ligand binding site of the real receptor.  Kind of like
making copy-cat antibodies by making anti-id and anti-anti-id
antibodies.   I believe that the theory behind copy-cat antibodies is more
sound than Blalock's theory. However, if my memory serves me correctly,
over a several year period, he claimed to have identified and cloned
receptors for 5 or more peptide ligands.  If the technique really worked,
one would think that lots of researchers would still be using it.

This is besides the obvious examples of genes that overlap on opposite
strands (like T3R and revErbA). 

SRLasky

> I agree with this use of antisense DNA because it is used within the context 
> of anti-sense RNA, which is also what Pam said. This might not be the best
> place to do this, but just to add some twigs to a burning house, I'd like to
> follow this with a quote from D. R. Forsdyke (I think s/he's lurking here).
> 
> @article{Forsdyke1995,
> author = "D. R. Forsdyke",
> title = "Sense in Antisense?",
> journal = "J. Mol. Evol.",
> volume = "41",
> pages = "582-586",
> comment = "antisense DNA and antisense proteins",
> year = "1995"}
> 
> "A DNA segment encoding a protein usually has a ``sense'' strand and a
> complementary ``antisense'' strand strand which acts as a template for RNA
> polymerase. Conventionally, the sense strand is considered to encode the
> protein since it has the same sequence as the mRNA."
> 
> No reference is given for the "convention", so I ask if this really IS
> convention? ...if so, does anyone have the reference? When it is stated that a
> DNA segment encoding a protein USUALLY has a ``sense'' strand, I'm
wondering if
> there are any cases where one doesn't?
> 
> Forsdyke further goes on the describe how ``antisense'' proteins are
translated
> from mRNA made that is equivalent to the ``antisense'' strand of DNA.
> Therefore, sense proteins are from the sense DNA strand and antisense proteins
> are made from the antisense DNA strand. To all this, I say BLECH! YUK! PHEWY!
> ...an antisense mRNA that encodes a protein???? Now I'm sick. That means it is
> an antisense/sense mRNA! Suppose I want to create a DNA strand that is
> antisense to that...this would be an antisense/sense/antisense = sense DNA
> added to lower translation of an antisense protein made from antisense RNA!
> I guess it all seems clear, but if you're not confused yet, I'll go on.
> 
>
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> * Paul N. Hengen, Ph.D.                          
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-- 
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Stephen R. Lasky Ph.D.   Brown U/Roger Williams Medical Center,  Providence, RI.   
Phone: 401-456-5672     Fax: 401-456-6569     e:mail: Stephen_Lasky at brown.edu
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America may be unique in being a country which has leapt from barbarism to decadence without touching civilization.  John O'Hara.
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