Protein-mediated RNA folding governs sequence-specific interactions between rotavirus genome segments

Borodavka, Alexander; Dykeman, Eric C.; Schrimpf, Waldemar; Lamb, Don C. (2017): Protein-mediated RNA folding governs sequence-specific interactions between rotavirus genome segments. In: eLife, Vol. 6, e27453

Abstract

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 nonstructural 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.

• Item Type: Journal article
• Research Centers: Center for Integrated Protein Science Munich (CIPSM)
• Subjects: 500 Science > 540 Chemistry
• ISSN: 2050-084X
• Language: English