RNA-guided assembly of Rev-RRE nuclear export complexes

Elife. 2014 Aug 27;3:e03656. doi: 10.7554/eLife.03656.

Abstract

HIV replication requires nuclear export of unspliced and singly spliced viral transcripts. Although a unique RNA structure has been proposed for the Rev-response element (RRE) responsible for viral mRNA export, how it recruits multiple HIV Rev proteins to form an export complex has been unclear. We show here that initial binding of Rev to the RRE triggers RNA tertiary structural changes, enabling further Rev binding and the rapid formation of a viral export complex. Analysis of the Rev-RRE assembly pathway using SHAPE-Seq and small-angle X-ray scattering (SAXS) reveals two major steps of Rev-RRE complex formation, beginning with rapid Rev binding to a pre-organized region presenting multiple Rev binding sites. This step induces long-range remodeling of the RNA to expose a cryptic Rev binding site, enabling rapid assembly of additional Rev proteins into the RNA export complex. This kinetic pathway may help maintain the balance between viral replication and maturation.DOI: http://dx.doi.org/10.7554/eLife.03656.001.

Keywords: HIV RRE-Rev complex; RNA nuclear export; SHAPE-Seq.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / genetics
  • Binding Sites
  • Cell Nucleus / metabolism*
  • Cell Nucleus / virology
  • Eukaryotic Cells / virology
  • HIV-1 / chemistry*
  • HIV-1 / metabolism
  • Humans
  • Molecular Sequence Data
  • RNA Folding
  • RNA Splicing
  • RNA Transport
  • RNA, Guide / chemistry*
  • RNA, Guide / metabolism
  • RNA, Viral / chemistry*
  • RNA, Viral / metabolism
  • Response Elements*
  • Scattering, Small Angle
  • Thermodynamics
  • Virus Replication
  • X-Ray Diffraction
  • rev Gene Products, Human Immunodeficiency Virus / chemistry*
  • rev Gene Products, Human Immunodeficiency Virus / metabolism

Substances

  • RNA, Guide
  • RNA, Viral
  • rev Gene Products, Human Immunodeficiency Virus