Conformational analysis of the 5' leader and the gag initiation site of Mo-MuLV RNA and allosteric transitions induced by dimerization.

Dimerization of genomic RNA is a key step in the retroviral life cycle and has been postulated to be involved in the regulation of translation, encapsidation and reverse transcription. Here, we have derived a secondary structure model of nucleotides upstream from psi and of the gag initiation region of Mo-MuLV RNA in monomeric and dimeric forms, using chemical probing, sequence comparison and computer prediction. The 5' domain is extensively base-paired and interactions take place between U5 and 5' leader sequences. The U5-PBS subdomain can fold in two mutually exclusive conformations: a very stable and extended helical structure (E form) in which 17 of the 18 nucleotides of the PBS are paired, or an irregular three-branch structure (B form) in which 10 nucleotides of the PBS are paired. The dimeric RNA adopts the B conformation. The monomeric RNA can switch from the E to the B conformation by a thermal treatment. If the E to B transition is associated to dimerization, it may facilitate annealing of the primer tRNAPro to the PBS by lowering the free energy required for melting the PBS. Furthermore, dimerization induces allosteric rearrangements around the SD site and the gag initiation region.