= It is probably best at this point to not worry how the proposed DNA
= gets to the protein. It isn't obvious, but it also isn't important
= (for now).
= About the only way to show a role for such a piece of DNA would be to
= find it, show that it works. If one has a guess as to what the DNA
= there might be some short-cuts. If one can isolate any DNA from prion
= preparations, that could be a starting point. If one suspects a
= particular small size, or size range, it is now practical to test all
= DNA of length 5 or 6 or so.
My guess is that it is a fungus RNA/DNA sequence. Some parasitic
fungus. Has the fungus of the ant disease Cordyceps Ascomycetes
Clavicipitacea been sequenced?
= You question my use of the term ligand or binding. But that is what
= you propose. If the DNA is not working by its coding function, the
= only way it could work is by binding to the prion, thus affecting its
Well, Bob, I not versed in the terms that you use. I can only use
what I know in simple language. If it is ligand and binding, then that
is what it is.
= Let us suppose that a particular prion conversion uses a small DNA
= molecule binding to the prion to "catalyze" the conversion. Nothing
= particularly wrong with this -- tho it can only be an idea until
= someone finds the DNA.
I suspect the Glover experiment found RNA/DNA because it could not
get 100% free of RNA/DNA.
And so the Glover experiment is a falsification of the Prusiner prion
= But a few important points...
= It is 'widely suspected' that some factor in addition to prion
= is needed for the conversion. You have mentioned the mysterious
= X. In yeast, a chaperone protein is needed in vivo.
I do not even know what a chaperone is.
= The essence of your proposal is that a small piece of DNA is factor x
= (or part of it). Yes?
You say that a protein can only be made by messenger RNA. If true,
then the factor x is a small piece of Messenger RNA.
= There is no particular advantage to using DNA. DNA does not have any
= properties that make it _especially_ suited for this. Proteins change
= shape all the time, binding oxygen, various chemicals in the body,
= proteins, DNA, whatever.
= It is quite plausible that different factors will be used in
= cases and under different conditions. In fact the yeast results
= (glover) in vitro do not seem to require any factor, whereas in vivo
= chaperone is required. This is all reasonable, since protein folding
= kinetics may be very sensitive to conditions. As I mentioned earlier,
= the glover expt should be best thought of as 'proof of principle'.
= direct relevance to anything is unclear.
The Glover experiment supported my theory that some RNA/DNA content
was there to cause the changes. Thus Glover experiment falsifies the
Prusiner prion theory.
= Mammalian prion diseases are very slow. Whatever it is that happens
= rare and/or slow. This is a difficulty in studying them!
= What would Prusiner or any 'reasonable biochemist' think of your
= proposal that DNA is factor X? Certainly consistent with the current
= standard model. No one would be bothered by it. They might be
= surprised, because I don't think we are expecting a small DNA
= to be there, to be playing this role. But if it were found to be
= so, fine, no problem. Would even be 'interesting'.
I need RNA/DNA to preserve the science of biology as the lowest
fundamental unit of biology to be the RNA/DNA for
reproduction/copy/replication. Not only for reproduction but also for
energy balance so that no laws of physics of thermodynamics are
= If a piece of DNA is needed for prion conversion in some cases, that
= would certainly be interesting. It would not change the basic story,
= but merely identify 'factor x' -- the detailed conditions needed for
= sense of the word (as animals do, or as DNA does). You are merely
= using DNA as a factor x, to catalyze the conversion. A protein might
= work, or maybe no catalyst is needed.
= see above. It is likely that their protein was essentially DNA free,
= but that is hard to prove. Further, it might be true for one prion
= not another.
= don't know.
= The new paper bennett posted needs follow up.
= doesn't seem likely. (And you must mean RNA here.) If something like
= this happened, presumably it involves the messenger RNA for the prion
= protein. By identifying a specific candidate nucleic acid, would be
= easier to test.
= maybe. The big problem is that DNA is not directly involved in making
= proteins; it is in a different part of the cell. RNA does not mend.
= well, that is not coding in the normal sense of the genetic role of
= DNA. It is simply one molecule affecting the shape of another, by
= binding. Proteins do that all the time.
= as discussed above, for binding, a small amount is enough.
= but that is a binding role; see above.There is no other way DNA
= affect the prion shape.
= well, that would be a stretch. A transposon is a piece of DNA that
= moves from one location of the chromosome to another.
My definition of a transposon is more broad. I define them as any
snippet or fragment of RNA or DNA that moves and performs a specific
function that is observable. Prion diseases are easily observable. And
this fungus RNA attachment to the protein molecule causes the prion
disease characteristics. It is movable. Let us not be bound to narrow
= I don't know of any case where a transposon is commonly associated
= with a particular disease. (My ignorance of that is not necessarily
= There are examples known where a particular mutation was shown to be
= due to a transposon. the first known case was reported in late 80s, i
= think. A child had a genetic disease, but analysis of the parents
= showed that neither carried the mutation. The mutation was due to a
= transposon. Thus the transposon must have 'jumped' during production
= of one of the germ cells for the child. (Can find reference, i
= A few examples of this have been shown. But of course, the disease is
= most commonly due to some mutation other than that caused by a
= transposon. BTW, a transpson jumping into a gene _usually_
= the gene.
= ==Bennett posted an item about a new article of concern (in vitro
= ==that is not infectious). All I know is what he posted. Sounds
= ==interesting, and I am sure it will be followed up. For the moment I
= ==think we just need to be aware of it, and watch to see what
= ==can think of simple reasons why it is not a 'problem.' But maybe it
= ==a problem; time will tell.
= =The simplest "not a problem" scenario is that the PrPres produced
= =the right configuration - since it's not possible to work out the
= =of PrPres we might never know ;-)
= This is a can of worms. Not all protease-resistant forms are
= necessarily equal. In fact, the notion of prion strains seems to
= depend on multiple biologically significant forms.
= The yeast in vitro prion conversion also need this reservation, I
= think. They are in a good sense 'proof of principal', but relevance
= harder to determine.
= =It does sound interesting, but I know only what I posted. I've been
= =the literature for a while with regards to prions. What made me sit
= =the Narang papers about the 1.2kb ssDNA. What is _that_ doing
= =it important? Is it somehow resistant to UV? What does it code for
= =not PrP according to GenBank).
= I'm going to try to find both this weekend.
= In the long run, the question will be whether the intriguing results
= suggested in these papers are reproducible.
I guess two experiments have now falsified Prusiner prion theory.
Both the Glover experiment and the 1.2kb ssDNA have rooted out nucleic
acids in prion proteins. Thus, prions contain attached nucleic acids.
Is the chemistry difficult to be able to recognize an attached
snippet of nucleic acid on the surface of a protein? How does one find
attached nucleic acid upon a protein molecule?