LSI Seminar Series: Blanton S. Tolbert, Ph.D., Case Western Reserve University

RNA and related retro viruses persist to pose serious threats to human health and global economies. Disease progression mediated by viral pathogenesis requires numerous intersections between host proteins and viral RNA (vRNA) elements. Host-vRNA complexes drive essential processes in the replication cycles of viruses; as such, they represent untapped targets for therapeutic intervention. Members of the heterogeneous nuclear ribonucleoprotein (hnRNP) family are cellular proteins often usurped by RNA viruses. The Tolbert lab studies the molecular mechanisms by which RNA viruses redirect hnRNPs to control viral gene expression. In this talk, Tolbert will describe solution NMR structures of conserved viral RNA elements that regulate splicing and translation. He further will show that conformational adaptation and slow protein motions are fundamental properties by which the cellular hnRNPs achieve cognate RNA recognition. In new and exciting results, the lab describes the NMR structure of a viral RNA-small molecule complex that inhibits viral replication by attenuating viral translation and shows that the small molecule inhibitor functions through a novel allosteric mechanism to increase the affinity of an RNA- protein complex. The collective knowledge this lab is producing suggests that protein- RNA cooperativity and mutual allostery manifest as idiosyncratic mechanisms that regulate viral gene expression.