A Solution to Limited Genomic Capacity: Using Adaptable Binding Surfaces to Assemble the Functional HIV Rev Oligomer on RNA

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Abstract

Many ribonucleoprotein (RNP) complexes assemble into large, organized structures in which protein subunits are positioned by interactions with RNA and other proteins. Here we demonstrate that HIV Rev, constrained in size by a limited viral genome, also forms an organized RNP by assembling a homo-oligomer on the Rev response element (RRE) RNA. Rev subunits bind cooperatively to discrete RNA sites using an oligomerization domain and an adaptable protein-RNA interface, forming a complex with 500-fold higher affinity than the tightest single interaction. High-affinity binding correlates strongly with RNA export activity. Rev utilizes different surfaces of its α-helical RNA-binding domain to recognize several low-affinity binding sites, including the well-characterized stem IIB site and an additional site in stem IA. We propose that adaptable RNA-binding surfaces allow the Rev oligomer to assemble economically into a discrete, stable RNP and provide a mechanistic role for Rev oligomerization during the HIV life cycle. © 2008 Elsevier Inc. All rights reserved.

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Daugherty, M. D., D’Orso, I., & Frankel, A. D. (2008). A Solution to Limited Genomic Capacity: Using Adaptable Binding Surfaces to Assemble the Functional HIV Rev Oligomer on RNA. Molecular Cell, 31(6), 824–834. https://doi.org/10.1016/j.molcel.2008.07.016

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