Quantitative Dissection of Dynamic RNA 3D Structural Ensembles that Regulate Viral Replication
Event Details
- Type
- Monday Lecture Series
- Speaker(s)
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Steve Bonilla, Ph.D., assistant professor and head, Laboratory of RNA Structural Biology and Biophysics, The Rockefeller University
- Speaker bio(s)
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RNAs are remarkably versatile molecules that can store genetic information and form functional three-dimensional (3D) structures. RNA viruses exploit this versatility, using RNAs that simultaneously encode viral proteins and fold into dynamic regulatory structures. These structures interact with viral and/or host proteins to regulate critical viral processes including translation, genome replication, and packaging. Despite their importance, the inherent flexibility of RNA presents significant challenges for structural characterization, limiting our understanding of their mechanisms. To overcome this, we employ an integrative approach combining cryo-electron microscopy (cryo-EM), computational simulations informed by Bayesian statistical methods, single-molecule FRET, and other biophysical approaches. We complement these structural methods with functional assays to validate our RNA 3D structural ensembles and map structure to function. Using this approach, we investigate dynamic RNA ensembles essential for flavivirus genome replication, revealing conserved RNA conformational states recognized by viral replication machinery. Additionally, we dissect multifunctional RNA conformational switches in positive-sense plant viruses to understand principles dictating the mechanism and evolution of RNA structures that coordinate multiple stages of viral life cycles. Ultimately, our integrative strategy aims to develop a predictive understanding of how RNA 3D structures regulate complex protein-mediated processes in cells and viruses.
Steve L. Bonilla earned his Ph.D. in the laboratory of Dan Herschlag at Stanford, investigating how RNA structures emerge in multistep folding pathways. As a postdoc with Jeffrey Kieft at the University of Colorado, he used single particle cryo-EM to follow the maturation of small, dynamic RNA structures encoded in viral genomes. In 2023 he joined Rockefeller as an assistant professor. Among several honors, Steve has received an Irma T. Hirschl/Monique Weill-Caulier Trust Research Award and an NIH Ruth L. Kirschten National Research Service Award. He was also named an HHMI Hanna H. Gray Fellow.
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- Open to
- Campus Only