title: HIV Rev response element (RRE) directs assembly of the Rev homooligomer into discrete asymmetric complexes.
abstract: RNA is a crucial structural component of many ribonucleoprotein (RNP) complexes, including the ribosome, spliceosome, and signal recognition particle, but the role of RNA in guiding complex formation is only beginning to be explored. In the case of HIV, viral replication requires assembly of an RNP composed of the Rev protein homooligomer and the Rev response element (RRE) RNA to mediate nuclear export of unspliced viral mRNAs. Assembly of the functional Rev-RRE complex proceeds by cooperative oligomerization of Rev on the RRE scaffold and utilizes both protein-protein and protein-RNA interactions to organize complexes with high specificity. The structures of the Rev protein and a peptide-RNA complex are known, but the complete RNP is not, making it unclear to what extent RNA defines the composition and architecture of Rev-RNA complexes. Here we show that the RRE controls the oligomeric state and solubility of Rev and guides its assembly into discrete Rev-RNA complexes. SAXS and EM data were used to derive a structural model of a Rev dimer bound to an essential RRE hairpin and to visualize the complete Rev-RRE RNP, demonstrating that RRE binding drives assembly of Rev homooligomers into asymmetric particles, reminiscent of the role of RNA in organizing more complex RNP machines, such as the ribosome, composed of many different protein subunits. Thus, the RRE is not simply a passive scaffold onto which proteins bind but instead actively defines the protein composition and organization of the RNP.
authors.affiliation: Chemistry and Chemical Biology Graduate Program, Graduate Group in Biophysics, Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Daugherty
authors.forename: David S
authors.initials: DS
authors.lastname: Booth
authors.forename: Bhargavi
authors.initials: B
authors.lastname: Jayaraman
authors.forename: Yifan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Alan D
authors.initials: AD
authors.lastname: Frankel
mesh_terms: D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D015694:Gene Products, rev / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006678:HIV / Q000235:genetics* / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020218:Response Elements; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D053838:Scattering, Small Angle; D014779:Virus Replication / Q000235:genetics
chemical_list: D015694:Gene Products, rev; D010455:Peptides; D011506:Proteins; D012333:RNA, Messenger; D012261:Ribonucleoproteins