FUNCTIONAL METASTABLE STRUCTURES IN RNA REPLICATION

We investigate the search in configuration space of an RNA molecule which folds onto itself as it is being assembled by sequential incorporation of nucleotides. The aim is to assess the role of transient folding intermediates in the regulation of RNA replication. We provide new evidence in support of the fact that major pauses in replication are induced by transitions between folded intermediates. This is done implementing a Monte Carlo simulation to reproduce a Markov process comprised of chain elongation and kinetically governed refolding events. The theoretical predictions are subsequently compared with pulse-chase electrophoretic experiments. This is done to show that the experimentally accessible rate of chain growth out of a pause site is identical to the predicted rate of the refolding event which has induced that pause. The results are illustrated with the example of template-instructed replication of MDV-1RNA.