Structural Plasticity of RRE Stem-Loop II Modulates Nuclear Export of HIV-1 RNA

• DOI: 10.1101/2025.02.20.639096
• Publication Date: 2025-02-26T19:25:18Z
• Authors: Manju Ojha; Lucia Hudson; Amanda Photenhauer; Trinity Zang; Lauren Lerew; Şölen Ekesan; Jason Daniels; Megan Nguyen; Hardik Paudyal; Darrin M. York; Melanie D. Ohi; Jan Marchant; Paul D. Bieniasz; Deepak Koirala
• Keywords: Nuclear export signal; Stem-loop

The Rev Response Element (RRE) forms an oligomeric complex with the viral protein to facilitate nuclear export of intron-retaining RNAs during late phase HIV-1 infection. However, our structural understanding this crucial virological process remains limited. In study, we determined several crystal structures intact RRE stem-loop II in two distinct conformations, performed negative-staining electron microscopy and molecular dynamics simulations, revealed that three-way junction RNA exhibits remarkable plasticity. Through vitro Rev-binding vivo Rev-activity assays using various mutants designed favor one conformers, demonstrated plasticity modulates binding oligomerization. Our findings illuminate emerging perspectives on dynamics-based regulation provide a framework for developing anti-HIV drugs target specific conformations.