Structural complexity of Dengue virus untranslated regions: cis-acting RNA motifs and pseudoknot interactions modulating functionality of the viral genome

Sztuba-Solinska, Joanna; Teramoto, Tadahisa; Rausch, Jason W.; Shapiro, Bruce A.; Padmanabhan, Radhakrishnan; Le Grice, Stuart F. J.

Pseudoknots are associated with a remarkably diverse range of biological activities, including translational control via internal ribosome entry site (48, 49) , ribosomal frameshifting (50, 51) , tRNA mimicry (47, (52) (53) (54) and temporal control of the termination of translation and initiation of genome replication (55) . It has been shown that 'flipping' of PK2 in the context of luciferase-based DENV2 replicon did not affect translation, but disrupted replication (8) , from which we conclude that the TL1/PK2 pseudoknot participates in regulation of DENV RNA synthesis. It is also possible that the TL1/PK2 pseudoknot might create a critical recognition element for host proteins. Supporting this notion, pseudoknots have been shown to cause distortion of A-form helices, creating a bend in the complex to provide a recognition site for ligands (56) . Also, it was shown that DEAD-box RNA helicase (DDX6) binds to both DBs and their corresponding PKs regions (43) . These authors suggested that the putative pseudoknots might provide assembly sites for DDX6, and that proper assembly of this protein had functional consequences for DENV replication.