The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform
Mutsuhito Ohno - One of the best experts on this subject based on the ideXlab platform.
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hiv 1 Rev Protein specifies the viral rna export pathway by suppressing tap nxf1 recruitment
Nucleic Acids Research, 2014Co-Authors: Ichiro Taniguchi, Naoto Mabuchi, Mutsuhito OhnoAbstract:Nuclear RNA export pathways in eukaryotes are often linked to the fate of a given RNA. Therefore, the choice of export pathway should be well-controlled to avoid an unfavorable effect on gene expression. Although some RNAs could be exported by more than one pathway, little is known about how the choice is regulated. This issue is highlighted when the human immunodeficiency virus type 1 (HIV-1) Rev Protein induces the export of singly spliced and unspliced HIV-1 transcripts. How these RNAs are exported is not well understood because such transcripts should have the possibility of utilizing CRM1-dependent export via Rev or cellular TAP/NXF1-dependent export via the transcription/export (TREX) complex, or both. Here we found that Rev suppressed TAP/NXF1-dependent export of model RNA substrates that recapitulated viral transcripts. In this effect, Rev interacted with the cap-binding complex and inhibited the recruitment of the TREX complex. Thus, Rev controls the identity of the factor occupying the cap-proximal region that determines the RNA export pathway. This ribonucleoProtein remodeling activity of Rev may favor viral gene expression.
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HIV-1 Rev Protein specifies the viral RNA export pathway by suppressing TAP/NXF1 recruitment
Nucleic acids research, 2014Co-Authors: Ichiro Taniguchi, Naoto Mabuchi, Mutsuhito OhnoAbstract:Nuclear RNA export pathways in eukaryotes are often linked to the fate of a given RNA. Therefore, the choice of export pathway should be well-controlled to avoid an unfavorable effect on gene expression. Although some RNAs could be exported by more than one pathway, little is known about how the choice is regulated. This issue is highlighted when the human immunodeficiency virus type 1 (HIV-1) Rev Protein induces the export of singly spliced and unspliced HIV-1 transcripts. How these RNAs are exported is not well understood because such transcripts should have the possibility of utilizing CRM1-dependent export via Rev or cellular TAP/NXF1-dependent export via the transcription/export (TREX) complex, or both. Here we found that Rev suppressed TAP/NXF1-dependent export of model RNA substrates that recapitulated viral transcripts. In this effect, Rev interacted with the cap-binding complex and inhibited the recruitment of the TREX complex. Thus, Rev controls the identity of the factor occupying the cap-proximal region that determines the RNA export pathway. This ribonucleoProtein remodeling activity of Rev may favor viral gene expression.
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NAR Breakthrough Article HIV-1 Rev Protein specifies the viral RNA export pathway by suppressing TAP/NXF1 recruitment
2014Co-Authors: Ichiro Taniguchi, Naoto Mabuchi, Mutsuhito OhnoAbstract:Nuclear RNA export pathways in eukaryotes are often linked to the fate of a given RNA. Therefore, the choice of export pathway should be wellcontrolled to avoid an unfavorable effect on gene expression. Although some RNAs could be exported by more than one pathway, little is known about how the choice is regulated. This issue is highlighted when the human immunodeficiency virus type 1 (HIV-1) Rev Protein induces the export of singly spliced and unspliced HIV-1 transcripts. How these RNAs are exported is not well understood because such transcripts should have the possibility of utilizing CRM1-dependent export via Rev or cellular TAP/NXF1-dependent export via the transcription/export (TREX) complex, or both. Here we found that Rev suppressed TAP/NXF1-dependent export of model RNA substrates that recapitulated viral transcripts. In this effect, Rev interacted with the cap-binding complex and inhibited the recruitment of the TREX complex. Thus, Rev controls the identity of the factor occupying the cap-proximal region that determines the RNA export pathway. This ribonucleoProtein remodeling activity of Rev may favor viral gene expression.
Ichiro Taniguchi - One of the best experts on this subject based on the ideXlab platform.
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hiv 1 Rev Protein specifies the viral rna export pathway by suppressing tap nxf1 recruitment
Nucleic Acids Research, 2014Co-Authors: Ichiro Taniguchi, Naoto Mabuchi, Mutsuhito OhnoAbstract:Nuclear RNA export pathways in eukaryotes are often linked to the fate of a given RNA. Therefore, the choice of export pathway should be well-controlled to avoid an unfavorable effect on gene expression. Although some RNAs could be exported by more than one pathway, little is known about how the choice is regulated. This issue is highlighted when the human immunodeficiency virus type 1 (HIV-1) Rev Protein induces the export of singly spliced and unspliced HIV-1 transcripts. How these RNAs are exported is not well understood because such transcripts should have the possibility of utilizing CRM1-dependent export via Rev or cellular TAP/NXF1-dependent export via the transcription/export (TREX) complex, or both. Here we found that Rev suppressed TAP/NXF1-dependent export of model RNA substrates that recapitulated viral transcripts. In this effect, Rev interacted with the cap-binding complex and inhibited the recruitment of the TREX complex. Thus, Rev controls the identity of the factor occupying the cap-proximal region that determines the RNA export pathway. This ribonucleoProtein remodeling activity of Rev may favor viral gene expression.
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HIV-1 Rev Protein specifies the viral RNA export pathway by suppressing TAP/NXF1 recruitment
Nucleic acids research, 2014Co-Authors: Ichiro Taniguchi, Naoto Mabuchi, Mutsuhito OhnoAbstract:Nuclear RNA export pathways in eukaryotes are often linked to the fate of a given RNA. Therefore, the choice of export pathway should be well-controlled to avoid an unfavorable effect on gene expression. Although some RNAs could be exported by more than one pathway, little is known about how the choice is regulated. This issue is highlighted when the human immunodeficiency virus type 1 (HIV-1) Rev Protein induces the export of singly spliced and unspliced HIV-1 transcripts. How these RNAs are exported is not well understood because such transcripts should have the possibility of utilizing CRM1-dependent export via Rev or cellular TAP/NXF1-dependent export via the transcription/export (TREX) complex, or both. Here we found that Rev suppressed TAP/NXF1-dependent export of model RNA substrates that recapitulated viral transcripts. In this effect, Rev interacted with the cap-binding complex and inhibited the recruitment of the TREX complex. Thus, Rev controls the identity of the factor occupying the cap-proximal region that determines the RNA export pathway. This ribonucleoProtein remodeling activity of Rev may favor viral gene expression.
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NAR Breakthrough Article HIV-1 Rev Protein specifies the viral RNA export pathway by suppressing TAP/NXF1 recruitment
2014Co-Authors: Ichiro Taniguchi, Naoto Mabuchi, Mutsuhito OhnoAbstract:Nuclear RNA export pathways in eukaryotes are often linked to the fate of a given RNA. Therefore, the choice of export pathway should be wellcontrolled to avoid an unfavorable effect on gene expression. Although some RNAs could be exported by more than one pathway, little is known about how the choice is regulated. This issue is highlighted when the human immunodeficiency virus type 1 (HIV-1) Rev Protein induces the export of singly spliced and unspliced HIV-1 transcripts. How these RNAs are exported is not well understood because such transcripts should have the possibility of utilizing CRM1-dependent export via Rev or cellular TAP/NXF1-dependent export via the transcription/export (TREX) complex, or both. Here we found that Rev suppressed TAP/NXF1-dependent export of model RNA substrates that recapitulated viral transcripts. In this effect, Rev interacted with the cap-binding complex and inhibited the recruitment of the TREX complex. Thus, Rev controls the identity of the factor occupying the cap-proximal region that determines the RNA export pathway. This ribonucleoProtein remodeling activity of Rev may favor viral gene expression.
Denis Archambault - One of the best experts on this subject based on the ideXlab platform.
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Identification of the nuclear and nucleolar localization signals of the Feline immunodeficiency virus Rev Protein.
Virus research, 2020Co-Authors: Claude Marchand, Guy Lemay, Denis ArchambaultAbstract:Abstract Lentivirus genomes code for a regulatory Protein essential for virus replication termed Rev. The Rev Protein binds to partially spliced and unspliced viral RNAs and mediates their nuclear export. Therefore, Rev possesses functional domains that enable its shuttling between the cytoplasm and the nucleus. The Feline immunodeficiency virus (FIV), a lentivirus, can lead to an immunodeficiency syndrome after a long incubation period, similar to that associated with the human immunodeficiency virus type 1 (HIV-1). The FIV Rev functional domains have been predicted only by homology with those of HIV-1 Rev. In the present study, the nuclear and nucleolar localization signals (NLS and NoLS, respectively) of the FIV Rev were examined. A series of FIV Rev deletion mutants fused to the enhanced green fluorescent Protein (EGFP) were used to localize the NLS in a region spanning amino acids (aa) 81–100. By using alanine substitution mutants, basic residues present between the amino acids (aa) 84–99 of the FIV Rev Protein sequence were identified to form the NLS, whereas those between aa 82–95 were associated with the NoLS function. These results further enhance our understanding of how Rev exerts its role in the replication cycle of lentiviruses.
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Characterization of Signal Sequences Determining the Nuclear/Nucleolar Import and Nuclear Export of the Caprine Arthritis-Encephalitis Virus Rev Protein
Viruses, 2020Co-Authors: Marlène Labrecque, Claude Marchand, Denis ArchambaultAbstract:Caprine arthritis-encephalitis virus (CAEV), a lentivirus, relies on the action of the Rev Protein for its replication. The CAEV Rev fulfills its function by allowing the nuclear exportation of partially spliced or unspliced viral mRNAs. In this study, we characterized the nuclear and nucleolar localization signals (NLS and NoLS, respectively) and the nuclear export signal (NES) of the CAEV Rev Protein. These signals are key actors in the nucleocytoplasmic shuttling of a lentiviral Rev Protein. Several deletion and alanine substitution mutants were generated from a plasmid encoding the CAEV Rev wild-type Protein that was fused to the enhanced green fluorescent Protein (EGFP). Following cell transfection, images were captured by confocal microscopy and the fluorescence was quantified in the different cell compartments. The results showed that the NLS region is localized between amino acids (aa) 59 to 75, has a monopartite-like structure and is exclusively composed of arginine residues. The NoLS was found to be partially associated with the NLS. Finally, the CAEV Rev Protein’s NES mapped between aa 89 to 101, with an aa spacing between the hydrophobic residues that was found to be unconventional as compared to that of other retroviral Rev/Rev-like Proteins.
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The Jembrana disease virus Rev Protein: Identification of nuclear and novel lentiviral nucleolar localization and nuclear export signals.
PloS one, 2019Co-Authors: Claude Marchand, Guy Lemay, Denis ArchambaultAbstract:The lentiviral Rev Protein, which is a regulatory Protein essential for virus replication, has been first studied in the human immunodeficiency virus type 1 (HIV-1). The main function of Rev is to mediate the nuclear exportation of viral RNAs. To fulfill its function, Rev shuttles between the cytoplasm and the nucleus. The Jembrana disease virus (JDV), a lentivirus, is the etiologic agent of the Jembrana disease which was first described in Bali cattle in Indonesia in 1964. Despite the high mortality rate associated with JDV, this virus remains poorly studied. Herein the subcellular distribution of JDV Rev, the nuclear and nucleolar localization signals (NLS and NoLS, respectively) and the nuclear export signal (NES) of the Protein were examined. JDV Rev fused to the enhanced green fluorescent Protein (EGFP) predominantly localized to the cytoplasm and nucleolus of transfected cells, as determined by fluorescence microscopy analyses. Through transfection of a series of deletion mutants of JDV Rev, it was possible to localize the NLS/NoLS region between amino acids (aa) 74 to 105. By substituting basic residues with alanine within this sequence, we demonstrated that the JDV Rev NLS encompasses aa 76 to 86, and is exclusively composed of arginine residues, whereas a bipartite NoLS was observed for the first time in any retroviral Rev/Rev-like Proteins. Finally, a NES was identified downstream of the NLS/NoLS and encompasses aa 116 to 128 of the JDV Rev Protein. The JDV Rev NES was found to be of the Protein kinase A inhibitor (PKI) class instead of the HIV-1 Rev class. It also corresponds to the most optimal consensus sequence of PKI NES and, as such, is novel among lentiviral Rev NES.
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b23 nucleophosmin interacts with bovine immunodeficiency virus Rev Protein and facilitates viral replication
Virology, 2018Co-Authors: Ana Maria Passoscastilho, Claude Marchand, Denis ArchambaultAbstract:The bovine immunodeficiency virus (BIV) Rev shuttling Protein contains nuclear/nucleolar localization signals and nuclear import/export mechanisms that are novel among lentivirus Rev Proteins. Several viral Proteins localize to the nucleolus, which may play a role in processes that are essential to the outcome of viral replication. Although BIV Rev localizes to the nucleoli of transfected/infected cells and colocalizes with one of its major Proteins, nucleophosmin (NPM1, also known as B23), the role of the nucleolus and B23 in BIV replication remains to be determined. Here, we demonstrate for the first time that BIV Rev interacts with nucleolar phosphoProtein B23 in cells. Using small interfering RNA (siRNA) technology, we show that depletion of B23 expression inhibits virus production by BIV-infected cells, indicating that B23 plays an important role in BIV replication. The interaction between Rev and B23 may represent a potential new target for the development of antiviral drugs against lentiviruses.
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B23/nucleophosmin interacts with bovine immunodeficiency virus Rev Protein and facilitates viral replication.
Virology, 2017Co-Authors: Ana Maria Passos-castilho, Claude Marchand, Denis ArchambaultAbstract:The bovine immunodeficiency virus (BIV) Rev shuttling Protein contains nuclear/nucleolar localization signals and nuclear import/export mechanisms that are novel among lentivirus Rev Proteins. Several viral Proteins localize to the nucleolus, which may play a role in processes that are essential to the outcome of viral replication. Although BIV Rev localizes to the nucleoli of transfected/infected cells and colocalizes with one of its major Proteins, nucleophosmin (NPM1, also known as B23), the role of the nucleolus and B23 in BIV replication remains to be determined. Here, we demonstrate for the first time that BIV Rev interacts with nucleolar phosphoProtein B23 in cells. Using small interfering RNA (siRNA) technology, we show that depletion of B23 expression inhibits virus production by BIV-infected cells, indicating that B23 plays an important role in BIV replication. The interaction between Rev and B23 may represent a potential new target for the development of antiviral drugs against lentiviruses.
Alan Cochrane - One of the best experts on this subject based on the ideXlab platform.
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Identification of small molecule modulators of HIV-1 Tat and Rev Protein accumulation
Retrovirology, 2017Co-Authors: Ahalya Balachandran, Raymond Wong, Peter Stoilov, Benjamin Blencowe, P. Richard Harrigan, Sandy Pan, Peter Y. K. Cheung, Alan CochraneAbstract:HIV-1 replication is critically dependent upon controlled processing of its RNA and the activities provided by its encoded regulatory factors Tat and Rev. A screen of small molecule modulators of RNA processing identified several which inhibited virus gene expression, affecting both relative abundance of specific HIV-1 RNAs and the levels of Tat and Rev Proteins. The screen for small molecules modulators of HIV-1 gene expression at the post-transcriptional level identified three (a pyrimidin-7-amine, biphenylcarboxamide, and benzohydrazide, designated 791, 833, and 892, respectively) that not only reduce expression of HIV-1 Gag and Env and alter the accumulation of viral RNAs, but also dramatically decrease Tat and Rev levels. Analyses of viral RNA levels by qRTPCR and RTPCR indicated that the loss of either Protein could not be attributed to changes in abundance of the mRNAs encoding these factors. However, addition of the proteasome inhibitor MG132 did result in significant restoration of Tat expression, indicating that the compounds are affecting Tat synthesis and/or degradation. Tests in the context of replicating HIV-1 in PBMCs confirmed that 791 significantly reduced virus replication. Parallel analyses of the effect of the compounds on host gene expression Revealed only minor changes in either mRNA abundance or alternative splicing. Subsequent tests suggest that 791 may function by reducing levels of the Tat/Rev chaperone Nap1. The three compounds examined (791, 833, 892), despite their lack of structural similarity, all suppressed HIV-1 gene expression by pReventing accumulation of two key HIV-1 regulatory factors, Tat and Rev. These findings demonstrate that selective disruption of HIV-1 gene expression can be achieved.
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Identification of small molecule modulators of HIV-1 Tat and Rev Protein accumulation
Retrovirology, 2017Co-Authors: Ahalya Balachandran, Raymond Wong, Peter Stoilov, Benjamin Blencowe, Peter Cheung, P. Richard Harrigan, Alan CochraneAbstract:Background HIV-1 replication is critically dependent upon controlled processing of its RNA and the activities provided by its encoded regulatory factors Tat and Rev. A screen of small molecule modulators of RNA processing identified several which inhibited virus gene expression, affecting both relative abundance of specific HIV-1 RNAs and the levels of Tat and Rev Proteins. Results The screen for small molecules modulators of HIV-1 gene expression at the post-transcriptional level identified three (a pyrimidin-7-amine, biphenylcarboxamide, and benzohydrazide, designated 791, 833, and 892, respectively) that not only reduce expression of HIV-1 Gag and Env and alter the accumulation of viral RNAs, but also dramatically decrease Tat and Rev levels. Analyses of viral RNA levels by qRTPCR and RTPCR indicated that the loss of either Protein could not be attributed to changes in abundance of the mRNAs encoding these factors. However, addition of the proteasome inhibitor MG132 did result in significant restoration of Tat expression, indicating that the compounds are affecting Tat synthesis and/or degradation. Tests in the context of replicating HIV-1 in PBMCs confirmed that 791 significantly reduced virus replication. Parallel analyses of the effect of the compounds on host gene expression Revealed only minor changes in either mRNA abundance or alternative splicing. Subsequent tests suggest that 791 may function by reducing levels of the Tat/Rev chaperone Nap1. Conclusions The three compounds examined (791, 833, 892), despite their lack of structural similarity, all suppressed HIV-1 gene expression by pReventing accumulation of two key HIV-1 regulatory factors, Tat and Rev. These findings demonstrate that selective disruption of HIV-1 gene expression can be achieved.
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Mutational analysis of the HIV-1 Rev Protein and its target sequence, the Rev responsive element.
Journal of acquired immune deficiency syndromes, 1991Co-Authors: Beidas S, P J Dillon, C A Rosen, Alan CochraneAbstract:The human immunodeficiency virus type 1 (HIV-1) Rev Protein is a positive posttranscriptional regulator of viral structural gene expression and essential for virus replication. Rev mediates its effects through interaction with an RNA target sequence, the Rev responsive element (RRE), present within the env mRNA. PRevious studies have shown that the basic stretch of amino acids are required for Rev's ability to bind RNA, whereas residues present near the carboxy terminus are essential for full biological activity. Deletion mutagenesis was used to define the minimal domain required for RNA binding and function. We found that amino acids 8 through 67 confer full binding activity, whereas full biological activity requires the presence of residues 8 through 83. The minimal RNA binding sequence of HIV-1 Rev also interacts and functions with the HIV-2 and SIV RRE elements, indicating that the same domain is responsible for the biological activity with different, but related viruses. Mutational analysis of the RRE was also carried out in an effort to further define elements crucial for its function. Our findings indicate that interaction with Rev involves a stretch of three G nucleotides present at the base of a stem loop structure pReviously shown to be critical for Rev binding. These results suggest that the high degree of secondary structure of the RRE RNA may serve as a guide to bring Rev in contact with a primary nucleotide sequence required for stable Protein-RNA association.
Naoto Mabuchi - One of the best experts on this subject based on the ideXlab platform.
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hiv 1 Rev Protein specifies the viral rna export pathway by suppressing tap nxf1 recruitment
Nucleic Acids Research, 2014Co-Authors: Ichiro Taniguchi, Naoto Mabuchi, Mutsuhito OhnoAbstract:Nuclear RNA export pathways in eukaryotes are often linked to the fate of a given RNA. Therefore, the choice of export pathway should be well-controlled to avoid an unfavorable effect on gene expression. Although some RNAs could be exported by more than one pathway, little is known about how the choice is regulated. This issue is highlighted when the human immunodeficiency virus type 1 (HIV-1) Rev Protein induces the export of singly spliced and unspliced HIV-1 transcripts. How these RNAs are exported is not well understood because such transcripts should have the possibility of utilizing CRM1-dependent export via Rev or cellular TAP/NXF1-dependent export via the transcription/export (TREX) complex, or both. Here we found that Rev suppressed TAP/NXF1-dependent export of model RNA substrates that recapitulated viral transcripts. In this effect, Rev interacted with the cap-binding complex and inhibited the recruitment of the TREX complex. Thus, Rev controls the identity of the factor occupying the cap-proximal region that determines the RNA export pathway. This ribonucleoProtein remodeling activity of Rev may favor viral gene expression.
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HIV-1 Rev Protein specifies the viral RNA export pathway by suppressing TAP/NXF1 recruitment
Nucleic acids research, 2014Co-Authors: Ichiro Taniguchi, Naoto Mabuchi, Mutsuhito OhnoAbstract:Nuclear RNA export pathways in eukaryotes are often linked to the fate of a given RNA. Therefore, the choice of export pathway should be well-controlled to avoid an unfavorable effect on gene expression. Although some RNAs could be exported by more than one pathway, little is known about how the choice is regulated. This issue is highlighted when the human immunodeficiency virus type 1 (HIV-1) Rev Protein induces the export of singly spliced and unspliced HIV-1 transcripts. How these RNAs are exported is not well understood because such transcripts should have the possibility of utilizing CRM1-dependent export via Rev or cellular TAP/NXF1-dependent export via the transcription/export (TREX) complex, or both. Here we found that Rev suppressed TAP/NXF1-dependent export of model RNA substrates that recapitulated viral transcripts. In this effect, Rev interacted with the cap-binding complex and inhibited the recruitment of the TREX complex. Thus, Rev controls the identity of the factor occupying the cap-proximal region that determines the RNA export pathway. This ribonucleoProtein remodeling activity of Rev may favor viral gene expression.
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NAR Breakthrough Article HIV-1 Rev Protein specifies the viral RNA export pathway by suppressing TAP/NXF1 recruitment
2014Co-Authors: Ichiro Taniguchi, Naoto Mabuchi, Mutsuhito OhnoAbstract:Nuclear RNA export pathways in eukaryotes are often linked to the fate of a given RNA. Therefore, the choice of export pathway should be wellcontrolled to avoid an unfavorable effect on gene expression. Although some RNAs could be exported by more than one pathway, little is known about how the choice is regulated. This issue is highlighted when the human immunodeficiency virus type 1 (HIV-1) Rev Protein induces the export of singly spliced and unspliced HIV-1 transcripts. How these RNAs are exported is not well understood because such transcripts should have the possibility of utilizing CRM1-dependent export via Rev or cellular TAP/NXF1-dependent export via the transcription/export (TREX) complex, or both. Here we found that Rev suppressed TAP/NXF1-dependent export of model RNA substrates that recapitulated viral transcripts. In this effect, Rev interacted with the cap-binding complex and inhibited the recruitment of the TREX complex. Thus, Rev controls the identity of the factor occupying the cap-proximal region that determines the RNA export pathway. This ribonucleoProtein remodeling activity of Rev may favor viral gene expression.