TY - JOUR TI - Protein-mediated RNA folding governs sequence-specific interactions between rotavirus genome segments AU - Borodavka, Alexander AU - Dykeman, Eric C AU - Schrimpf, Waldemar AU - Lamb, Don C A2 - Ha, Taekjip VL - 6 PY - 2017 DA - 2017/09/18 SP - e27453 C1 - eLife 2017;6:e27453 DO - 10.7554/eLife.27453 UR - https://doi.org/10.7554/eLife.27453 AB - Segmented RNA viruses are ubiquitous pathogens, which include influenza viruses and rotaviruses. A major challenge in understanding their assembly is the combinatorial problem of a non-random selection of a full genomic set of distinct RNAs. This process involves complex RNA-RNA and protein-RNA interactions, which are often obscured by non-specific binding at concentrations approaching in vivo assembly conditions. Here, we present direct experimental evidence of sequence-specific inter-segment interactions between rotavirus RNAs, taking place in a complex RNA- and protein-rich milieu. We show that binding of the rotavirus-encoded non-structural protein NSP2 to viral ssRNAs results in the remodeling of RNA, which is conducive to formation of stable inter-segment contacts. To identify the sites of these interactions, we have developed an RNA-RNA SELEX approach for mapping the sequences involved in inter-segment base-pairing. Our findings elucidate the molecular basis underlying inter-segment interactions in rotaviruses, paving the way for delineating similar RNA-RNA interactions that govern assembly of other segmented RNA viruses. KW - Rotavirus KW - RNA-RNA interactions KW - RNA folding KW - Virus assembly KW - Fluorescence Cross-Correlation Spectroscopy JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -