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FOLDING PATHWAYS OF RNA BY CATION CONDENSATION

Ursula Perez-Salas, Division 856, Materials Science and Engineering Laboratory

Condensation of counterions around the RNA reduces the phosphate charge by 75-95%. This
reduction of the electrostatic repulsion between phosphates after the counterions condense
triggers a collapse of the chain to a more compact structure that contains some native and
some non-native interactions.  This state is termed an intermediate (or molten globule) as
it has a (relatively) compact structure but is not biologically active. The native or
catalytic structure is stabilized by the divalent metal ions Mg+2 or Mn2+.

From a theoretical stand point, the relationship between the extent of charge neutralization
and the dimension of the RNA (Rg) leads to the prediction that Rg decreases in proportion to
1/Z2, because multivalent ions are more efficient condensing agents than monovalent ions.
Hence, more compact structures are obtained with multivalent than with monovalent ions.

Using small angle neutron scattering it was observed that the radius of gyration, Rg, of the
Azoarcus ribozyme collapsed to different compact forms using 1, 2 and 3 valence salts at
different concentrations.