TY - JOUR T1 - The HIV-1 ribonucleoprotein dynamically regulates its condensate behavior and drives acceleration of protease activity through membrane-less granular phase-separation JF - bioRxiv DO - 10.1101/528638 SP - 528638 AU - Sébastien Lyonnais AU - S. Kashif Sadiq AU - Cristina Lorca-Oró AU - Laure Dufau AU - Sara Nieto-Marquez AU - Tuixent Escriba AU - Natalia Gabrielli AU - Xiao Tan AU - Mohamed Ouizougun-Oubari AU - Josephine Okoronkwo AU - Michèle Reboud-Ravaux AU - José Maria Gatell AU - Roland Marquet AU - Jean-Christophe Paillart AU - Andreas Meyerhans AU - Carine Tisné AU - Robert J. Gorelick AU - Gilles Mirambeau Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/01/28/528638.abstract N2 - A growing number of studies indicate that mRNAs and long ncRNAs can affect protein populations by assembling dynamic ribonucleoprotein (RNP) granules. These phase-separated molecular ‘sponges’, stabilized by quinary (transient and weak) interactions, control proteins involved in numerous biological functions. Retroviruses such as HIV-1 form by self-assembly when their genomic RNA (gRNA) traps Gag and GagPol polyprotein precursors. Infectivity requires extracellular budding of the particle followed by maturation, an ordered processing of ~2400 Gag and ~120 GagPol by viral protease (PR). This leads to a condensed gRNA-NCp7 nucleocapsid and a CAp24-self-assembled capsid surrounding the RNP. The choreography by which all of these components dynamically interact during virus maturation is one of the missing milestones to fully depict the HIV life cycle. Here, we describe how HIV-1 has evolved a dynamic RNP granule with successive weak-strong-moderate quinary NC-gRNA networks during the sequential processing of the GagNC domain. We also reveal two palindromic RNA-binding triads on NC, KxxFxxQ and QxxFxxK, that provide quinary NC-gRNA interactions. Consequently, the nucleocapsid complex appears properly aggregated for capsid reassembly and reverse transcription, mandatory processes for viral infectivity. We show that PR is sequestered within this RNP and drives its maturation/condensation within minutes, this process being most effective at the end of budding. We anticipate such findings will stimulate further investigations of quinary interactions and emergent mechanisms in crowded environments throughout the wide and growing array of RNP granules. ER -