Ap. Gultyaev et al., DYNAMIC COMPETITION BETWEEN ALTERNATIVE STRUCTURES IN VIROID RNAS SIMULATED BY AN RNA FOLDING ALGORITHM, Journal of Molecular Biology, 276(1), 1998, pp. 43-55
The folding pathways of viroid RNAs were studied using computer simula
tions by the genetic algorithm for RNA folding. The folding simulation
s were performed for PSTVd RNAs of both polarities, using the wild-typ
e sequence and some previously known mutants with suggested changes in
the stable or metastable structures. It is shown that metastable mult
ihairpin foldings in the minus strand replicative intermediates are es
tablished due to the specific folding pathway that ensures the absence
of the most stable rod-like structure. Simulations of the PSTVd minus
strand folding during transcription reveal a metastable hairpin, form
ed in the left terminal domain region of the PSTVd. Despite high seque
nce variability, this hairpin is conserved in all known large viroids
of both subgroups of PSTVd type, and is presumably necessary to guide
the folding of the HPII. hairpin which is functional in the minus stra
nd. The folding simulations are able to demonstrate the changes in the
balance between metastable and stable structures in mutant PSTVd RNAs
. The stable rod-like structure of the circular viroid (+) RNA is also
folded via a dynamic folding pathway. Furthermore, the simulations sh
ow that intermediate steps iri the forced evolution of a shortened PST
Vd replicon may be reconstructed by a mechanistic model of different f
olding pathway requirements in plus-and minus-strand RNAs. Thus the fo
rmation of viroid RNA structure strongly depends on dynamics of compet
ition between alternative RNA structures. This also suggests that the
replication efficiency of viroid sequences may be estimated by a simul
ation of the folding process. (C) 1998 Academic Press Limited.