RNA loop-loop interactions as dynamic functional motifs

Abstract

RNA loop-loop interactions are frequently used to trigger initial recognition between two RNA molecules. In this review, we present selected well-documented cases that illustrate the diversity of biological processes using RNA loop-loop recognition properties. The first one is related to natural antisense RNAs that play a variety of regulatory functions in bacteria and their extra-chromosomal elements. The second one concerns the dimerization of HIV-1 genomic RNA, which is responsible for the encapsidation of a diploid RNA genome. The third one concerns RNA interactions involving double-loop interactions. These are used by the bicoid mRNA to form dimers, a property that appears to be important for mRNA localization in drosophila embryo, and by bacteriophage phi29 pRNA which forms hexamers that participate in the translocation of the DNA genome through the portal vertex of the capsid. Despite the high diversity of systems and mechanisms, some common features can be highlighted. (1) Efficient recognition requires rapid bi-molecular binding rates, regardless of the RNA pairing scheme. (2) The initial recognition is favored by particular conformations of the loops enabling a proper presentation of nucleotides (generally a restricted number) that initiate the recognition process. (3) The fate of the initial reversible loop-loop complex is dictated by both functional and structural constraints. RNA structures have evolved either to "freeze" the initial complex, or to convert it into a more stable one, which involves propagation of intermolecular interactions along topologically feasible pathways. Stabilization of the initial complex may also be assisted by proteins and/or formation of additional contacts.