The HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during Maturation
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...
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oai:doaj.org-article:35afacfa36b0410b8a99db77793c381e2021-11-25T19:14:28ZThe HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during Maturation10.3390/v131123121999-4915https://doaj.org/article/35afacfa36b0410b8a99db77793c381e2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2312https://doaj.org/toc/1999-4915A 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 the 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.Sébastien LyonnaisS. Kashif SadiqCristina Lorca-OróLaure DufauSara Nieto-MarquezTuixent EscribàNatalia GabrielliXiao TanMohamed Ouizougun-OubariJosephine OkoronkwoMichèle Reboud-RavauxJosé Maria GatellRoland MarquetJean-Christophe PaillartAndreas MeyerhansCarine TisnéRobert J. GorelickGilles MirambeauMDPI AGarticleHIV-1nucleocapsidRNAliquid–liquid phase separationproteasemolecular dynamicsMicrobiologyQR1-502ENViruses, Vol 13, Iss 2312, p 2312 (2021) |
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HIV-1 nucleocapsid RNA liquid–liquid phase separation protease molecular dynamics Microbiology QR1-502 |
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HIV-1 nucleocapsid RNA liquid–liquid phase separation protease molecular dynamics Microbiology QR1-502 Sébastien Lyonnais S. Kashif Sadiq Cristina Lorca-Oró Laure Dufau Sara Nieto-Marquez Tuixent Escribà Natalia Gabrielli Xiao Tan Mohamed Ouizougun-Oubari Josephine Okoronkwo Michèle Reboud-Ravaux José Maria Gatell Roland Marquet Jean-Christophe Paillart Andreas Meyerhans Carine Tisné Robert J. Gorelick Gilles Mirambeau The HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during Maturation |
description |
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 the 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. |
format |
article |
author |
Sébastien Lyonnais S. Kashif Sadiq Cristina Lorca-Oró Laure Dufau Sara Nieto-Marquez Tuixent Escribà Natalia Gabrielli Xiao Tan Mohamed Ouizougun-Oubari Josephine Okoronkwo Michèle Reboud-Ravaux José Maria Gatell Roland Marquet Jean-Christophe Paillart Andreas Meyerhans Carine Tisné Robert J. Gorelick Gilles Mirambeau |
author_facet |
Sébastien Lyonnais S. Kashif Sadiq Cristina Lorca-Oró Laure Dufau Sara Nieto-Marquez Tuixent Escribà Natalia Gabrielli Xiao Tan Mohamed Ouizougun-Oubari Josephine Okoronkwo Michèle Reboud-Ravaux José Maria Gatell Roland Marquet Jean-Christophe Paillart Andreas Meyerhans Carine Tisné Robert J. Gorelick Gilles Mirambeau |
author_sort |
Sébastien Lyonnais |
title |
The HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during Maturation |
title_short |
The HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during Maturation |
title_full |
The HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during Maturation |
title_fullStr |
The HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during Maturation |
title_full_unstemmed |
The HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during Maturation |
title_sort |
hiv-1 nucleocapsid regulates its own condensation by phase-separated activity-enhancing sequestration of the viral protease during maturation |
publisher |
MDPI AG |
publishDate |
2021 |
url |
https://doaj.org/article/35afacfa36b0410b8a99db77793c381e |
work_keys_str_mv |
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