scholarly journals N-Methylation as a Strategy for Enhancing the Affinity and Selectivity of RNA-binding Peptides: Application to the HIV-1 Frameshift-Stimulating RNA

2015 ◽  
Vol 11 (1) ◽  
pp. 88-94 ◽  
Author(s):  
Thomas A. Hilimire ◽  
Ryan P. Bennett ◽  
Ryan A. Stewart ◽  
Pablo Garcia-Miranda ◽  
Alex Blume ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Peptides ◽  
Hiv 1

scholarly journals Characterization of a human TAR RNA-binding protein that activates the HIV-1 LTR

Science ◽  
1991 ◽  
Vol 251 (5001) ◽  
pp. 1597-1600 ◽  
Author(s):  
A Gatignol ◽  
A Buckler-White ◽  
B Berkhout ◽  
K. Jeang
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Tar Rna ◽  
Hiv 1

TAR-Independent Activation of HIV-1 Requires the Activation Domain but Not the RNA-Binding Domain of Tat

Virology ◽  
1993 ◽  
Vol 195 (2) ◽  
pp. 780-785 ◽  
Author(s):  
J.Paul Taylor ◽  
Mondira Kundu ◽  
Kamel Khalili
Keyword(s):  
Rna Binding ◽  
Binding Domain ◽  
Activation Domain ◽  
Rna Binding Domain ◽  
Hiv 1

scholarly journals Sequence analysis of an artificial family of RNA-binding peptides

2009 ◽  
Vol 11 (11) ◽  
pp. 2688-2696 ◽  
Author(s):  
Jeffrey E. Barrick ◽  
Richard W. Roberts
Keyword(s):  
Sequence Analysis ◽  
Rna Binding ◽  
Binding Peptides

scholarly journals TAR-RNA binding by HIV-1 Tat protein is selectively inhibited by its L-enantiomer

1998 ◽  
Vol 26 (12) ◽  
pp. 2886-2890 ◽  
Author(s):  
A. Garbesi ◽  
F. Hamy ◽  
M. Maffini ◽  
G. Albrecht ◽  
T. Klimkait
Keyword(s):  
Rna Binding ◽  
Tat Protein ◽  
Tar Rna ◽  
Hiv 1

scholarly journals The HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during Maturation

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2312
Author(s):  
Sébastien Lyonnais ◽  
S. Kashif Sadiq ◽  
Cristina Lorca-Oró ◽  
Laure Dufau ◽  
Sara Nieto-Marquez ◽  
...  
Keyword(s):  
Self Assembly ◽  
Rna Binding ◽  
Weak Interactions ◽  
Biological Functions ◽  
Viral Protease ◽  
Virus Maturation ◽  
Sequential Processing ◽  
Rnp Granules ◽  
Crowded Environments ◽  
Hiv 1

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.

scholarly journals Visualizing the translation and packaging of HIV-1 full-length RNA

2020 ◽  
Vol 117 (11) ◽  
pp. 6145-6155 ◽  
Author(s):  
Jianbo Chen ◽  
Yang Liu ◽  
Bin Wu ◽  
Olga A. Nikolaitchik ◽  
Preeti R. Mohan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Molecule ◽  
Rna Binding ◽  
Virus Assembly ◽  
Full Length ◽  
Rna Molecules ◽  
Rna Translation ◽  
Translation Template ◽  
A Genome ◽  
Hiv 1

HIV-1 full-length RNA (HIV-1 RNA) plays a central role in viral replication, serving as a template for Gag/Gag-Pol translation and as a genome for the progeny virion. To gain a better understanding of the regulatory mechanisms of HIV-1 replication, we adapted a recently described system to visualize and track translation from individual HIV-1 RNA molecules in living cells. We found that, on average, half of the cytoplasmic HIV-1 RNAs are being actively translated at a given time. Furthermore, translating and nontranslating RNAs are well mixed in the cytoplasm; thus, Gag biogenesis occurs throughout the cytoplasm without being constrained to particular subcellular locations. Gag is an RNA binding protein that selects and packages HIV-1 RNA during virus assembly. A long-standing question in HIV-1 gene expression is whether Gag modulates HIV-1 RNA translation. We observed that despite its RNA-binding ability, Gag expression does not alter the proportion of translating HIV-1 RNA. Using single-molecule tracking, we found that both translating and nontranslating RNAs exhibit dynamic cytoplasmic movement and can reach the plasma membrane, the major HIV-1 assembly site. However, Gag selectively packages nontranslating RNA into the assembly complex. These studies illustrate that although HIV-1 RNA serves two functions, as a translation template and as a viral genome, individual RNA molecules carry out only one function at a time. These studies shed light on previously unknown aspects of HIV-1 gene expression and regulation.

HIV-1 TAR RNA-binding proteins control TAT activation of translation in Xenopus oocytes.

1993 ◽  
Vol 7 (1) ◽  
pp. 214-222 ◽  
Author(s):  
M Braddock ◽  
R Powell ◽  
A D Blanchard ◽  
A J Kingsman ◽  
S M Kingsman
Keyword(s):  
Xenopus Oocytes ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Tar Rna ◽  
Hiv 1

scholarly journals Relationships between MA-RNA Binding in Cells and Suppression of HIV-1 Gag Mislocalization to Intracellular Membranes

2019 ◽  
Vol 93 (23) ◽  
Author(s):  
Dishari Thornhill ◽  
Balaji Olety ◽  
Akira Ono
Keyword(s):  
Rna Binding ◽  
Fluorescent Protein ◽  
Yellow Fluorescent Protein ◽  
Membrane Binding ◽  
Intracellular Membrane ◽  
Intracellular Membranes ◽  
Specific Localization ◽  
Basic Region ◽  
Hiv 1 ◽  
In Cells

ABSTRACT The HIV-1 Gag matrix (MA) domain mediates the localization of Gag to the plasma membrane (PM), the site for infectious virion assembly. The MA highly basic region (MA-HBR) interacts with phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2], a PM-specific acidic lipid. The MA-HBR also binds RNAs. To test whether acidic lipids alone determine PM-specific localization of Gag or whether MA-RNA binding also plays a role, we compared a panel of MA-HBR mutants that contain two types of substitutions at MA residues 25 and 26 or residues 29 and 31: Lys→Arg (KR) (25/26KR and 29/31KR) and Lys→Thr (KT) (25/26KT and 29/31KT). Consistent with the importance of the HBR charge in RNA binding, both KT mutants failed to bind RNA via MA efficiently, unlike the corresponding KR mutants. Both 25/26KT Gag-yellow fluorescent protein (YFP) and 29/31KT Gag-YFP bound nonspecifically to the PM and intracellular membranes, presumably via the myristoyl moiety and remaining MA basic residues. In contrast, 25/26KR Gag-YFP bound specifically to the PM, suggesting a role for the total positive charge and/or MA-bound RNA in navigating Gag to the PM. Unlike 29/31KT Gag-YFP, 29/31KR Gag-YFP was predominantly cytosolic and showed little intracellular membrane binding despite having a higher HBR charge. Therefore, it is likely that MA-RNA binding blocks promiscuous Gag membrane binding in cells. Notably, the introduction of a heterologous multimerization domain restored PI(4,5)P2-dependent PM-specific localization for 29/31KR Gag-YFP, suggesting that the blocking of PM binding is more readily reversed than that of intracellular membrane binding. Altogether, these cell-based data support a model in which MA-RNA binding ensures PM-specific localization of Gag via suppression of nonspecific membrane binding. IMPORTANCE The PM-specific localization of HIV-1 Gag is a crucial early step in infectious progeny production. The interaction between the MA highly basic region (MA-HBR) of Gag and the PM-specific lipid PI(4,5)P2 is critical for Gag localization to the PM. Additionally, in vitro evidence has indicated that MA-RNA binding prevents nonspecific binding of Gag to non-PI(4,5)P2-containing membranes. However, cell-based evidence supporting a role for HIV-1 MA-RNA binding in PM-specific subcellular localization has been scarce; thus, it remained possible that in cells, just the high basic charge or the PI(4,5)P2 binding ability is sufficient for MA to direct Gag specifically to the PM. The present study reveals for the first time an excellent correlation between RNA binding of the MA-HBR and inhibition of promiscuous Gag localization, both within the cells, and thereby provides cell-based evidence supporting a mechanism in which HIV-1 MA binding to RNA ensures the specific localization of Gag to the PM.

Inhibition of Rev-mediated HIV-1 expression by an RNA binding protein encoded by the interferon-inducible 9-27 gene

Science ◽  
1993 ◽  
Vol 259 (5099) ◽  
pp. 1314-1318 ◽  
Author(s):  
P Constantoulakis ◽  
M Campbell ◽  
B. Felber ◽  
G Nasioulas ◽  
E Afonina ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Hiv 1

scholarly journals Human Immunodeficiency Virus Type 1 Vif Protein Is an Integral Component of an mRNP Complex of Viral RNA and Could Be Involved in the Viral RNA Folding and Packaging Process

2000 ◽  
Vol 74 (18) ◽  
pp. 8252-8261 ◽  
Author(s):  
Hui Zhang ◽  
Roger J. Pomerantz ◽  
Geethanjali Dornadula ◽  
Yong Sun
Keyword(s):  
Human Immunodeficiency Virus ◽  
Rna Binding ◽  
Viral Rna ◽  
Immunodeficiency Virus ◽  
Mrnp Complex ◽  
Rna Interaction ◽  
Vif Protein ◽  
Hiv 1

ABSTRACT Virion infectivity factor (Vif) is a protein encoded by human immunodeficiency virus types 1 and 2 (HIV-1 and -2) and simian immunodeficiency virus, plus other lentiviruses, and is essential for viral replication either in vivo or in culture for nonpermissive cells such as peripheral blood lymphoid cells, macrophages, and H9 T cells. Defects in the vif gene affect virion morphology and reverse transcription but not the expression of viral components. It has been shown that Vif colocalizes with Gag in cells and Vif binds to the NCp7 domain of Gag in vitro. However, it seems that Vif is not specifically packaged into virions. The molecular mechanism(s) for Vif remains unknown. In this report, we demonstrate that HIV-1 Vif is an RNA-binding protein and specifically binds to HIV-1 genomic RNA in vitro. Further, Vif binds to HIV-1 RNA in the cytoplasm of virus-producing cells to form a 40S mRNP complex. Coimmunoprecipitation and in vivo UV cross-linking assays indicated that Vif directly interact with HIV-1 RNA in the virus-producing cells. Vif-RNA binding could be displaced by Gag-RNA binding, suggesting that Vif protein in the mRNP complex may mediate viral RNA interaction with HIV-1 Gag precursors. Furthermore, we have demonstrated that these Vif mutants that lose the RNA binding activity in vitro do not supportvif-deficient HIV-1 replication in H9 T cells, suggesting that the RNA binding capacity of Vif is important for its function. Further studies regarding Vif-RNA interaction in virus-producing cells will be important for studying the function of Vif in the HIV-1 life cycle.

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