User talk:ElNando888/Blog/Outsider

Double T Stacking Example

Nando, I find this extremely interesting.  What is the PDB entry and positions?

I've been thinking about how T stacking, in combination with more common stacking, might create enough energetic non-linearity in the poly(A) molecule to account for the fact that any particular lab sequence seems to form into a well-defined structure (i.e. not enough variation among the thousands of instances of that sequence to turn all the SHAPE values into "average" values), and yet the formations look so different for molecules with only slightly different sequences at the 3' end of the poly(A).

----

Hi Omei,

I added the source information on the page itself, below the picture.

As for the poly(A) mystery, I've been having the wildest ideas myself for many weeks, T-shaped stacking was one of them. I never managed to model something that could come close to possibly explaining the observed phenomenon. Always a problem with the construct. Either some of the bases should appear reactive, or the construct would not have the terminal 6 reactive ones, etc. At this point, I really wish we could apply at least NMR. I suggested titration on the forum, but it would just tell us whether cations are involved or not. Sigh...

-- ElNando888 (talk) 22:15, 20 September 2013 (UTC)

----

FWIW, my interpretation of the 6 or so reactive ones is that the backbone of the poly(A) has such a radically different configuration (I'll call it the ζ-configuration) from the α-helix that there has to be a multiiple-nucleotide  transition region from the α-helix of heterogeneous RNA to the ζ-configuration of the poly(A).

Omei (talk) 00:18, 21 September 2013 (UTC)

----

Here's a hypothesis for the string of reactive A's.

Did you have metal slinky as a kid?  I did, and I also had four younger siblings who would play with it and get it all tangled up.  One way it could get tangled would be for a section of the slinky to change from a right-handed helix to a left handed one.  (Or maybe it was the other way around.)  When this happened, there would be a big loop where the two helices came together and the slinky had to transition between the two conformations.  That loop, as I remember, had about the same circumference as the normal helical sections.  And the two helicial sections would want to be anti-parallel.

So suppose the ζ-configuration was a left-handed helix.  The slinky's transitional loop would correspond to a loop of exposed A'a at the transitions between helices.  The poly(A) helix would be anti-parallel, and thus adjacent to, the double stranded stem.  This proximity would provide a easy mechanism for small changes in the stem to affect the poly(A) helix many base poistions away.  And the possible interactions between a normal double stranded right-handed helix and an adjacent single stranded left hand helix are likely to include ones unlike any of those that have been well characterized.

After thinking of this possibility, I did a quick search for the existence of a left-handed RNA helix.  I found references to a Z-RNA, a synthetic left-handed double stranded RNA helix, and a natural left-handed single stranded nucleoprotein-RNA complex.  So a left-handed helix for poly(A) doesn't seem completely crazy.

Omei (talk) 05:18, 21 September 2013 (UTC)

----