Research

Long-range RNA tertiary interactions dynamically regulate biological processes such as mRNA translation and viral replication. Two viruses that utilize this mechanism to control multiple steps of their replication cycle are HIV-1 and dengue virus. RNA tertiary interactions in the HIV-1 genome regulate reverse transcription by facilitating 5′-3′ strand transfer. In flaviviruses such as dengue and Zika viruses that are important human pathogens, vRNA cyclization through base pairing between the 5′-UTR and 3′-UTR is thought to facilitate the transition between viral translation and replication. This elaborate switching mechanism involves RNA conformational rearrangements, recruitment of viral proteins, and dynamic remodeling of the protein-RNA complex. We are using biochemical assays and single-molecule fluorescence microscopy to understand the detailed mechanisms underlying these fundamental steps of viral life cycles.

Figure 12

Figure 12 Using FRET to explore long-range structures of viral RNAs, such as Dengue, that have been proposed to circularize through 5’ to 3’ end interactions. 

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Figure 12 Using combinations of FRET and other imaging modalities to understand the architecture of HIV viral RNA packaged in capsids. HIV RNA is dimeric, and during reverse transcription, the ends of the viral RNA must come in proximity to allow the process to proceed.  FRET measurements within capsids will determine the dynamic structure of HIV genomic RNA and its linkage to reverse transcription.