Salt-Dependent Self-Association of Trinucleotide Repeat RNA Sequences.

Repeat RNA sequences self-associate to form condensates. Simulations of a coarse-grained single-interaction site model for (CAG) n ( n = 30 and 31) show that the salt-dependent free energy gap, Δ G S , between the ground (perfect hairpin) and the excited state (slipped hairpin (SH) with one CAG overhang) of the monomer for ( n even) is the primary factor that determines the rates and yield of self-assembly. For odd n , the free energy ( G S ) of the ground state, which is an SH, is used to predict the self-association kinetics. As the monovalent salt concentration, C S , increases, Δ G S and G S increase, which decreases the rates of dimer formation. In contrast, Δ G S for shuffled sequences, with the same length and sequence composition as (CAG) 31 , is larger, which suppresses their propensities to aggregate. Although demonstrated explicitly for (CAG) polymers, the finding of inverse correlation between the free energy gap and RNA aggregation is general.