Noncoexisting structural elements in catalytic pre-messenger RNA's

We simulate the sequential folding of an autocatalytic pre-mRNA of group I revealing a scenario where core elements exert their function on intramolecular substrates as they are being generated. Our results indicate that the interactions shaping the 3'-substrate do not coexist with those shaping the 5'-substrate, but form after 5'-cleavage has occurred. This chronology of events is shown to be required for ribozyme function and quite universal in group I introns, since it is based on a competition of conserved helical stems. Preliminary probes rooted in site-directed mutagenesis are invoked to further validate the results.