The Experts below are selected from a list of 129 Experts worldwide ranked by ideXlab platform

Elyanne Gault - One of the best experts on this subject based on the ideXlab platform.

  • The interactome analysis of the Respiratory Syncytial Virus Protein M2-1 suggests a new role in viral mRNA metabolism post- transcription
    Scientific Reports, 2019
    Co-Authors: Camille Bouillier, Aurore Desquesnes, Sabine Blouquit-laye, Gina Cosentino, Thibaut Léger, Jean-françois Eleouet, Charles-adrien Richard, Vincent Rincheval, Delphine Sitterlin, Elyanne Gault
    Abstract:

    Human respiratory syncytial virus (RSV) is a globally prevalent negative-stranded RNA virus, which can cause life-threatening respiratory infections in young children, elderly people and immunocompromised patients. Its transcription termination factor M2-1 plays an essential role in viral transcription, but the mechanisms underpinning its function are still unclear. We investigated the cellular interactome of M2-1 using green fluorescent Protein (GFP)-trap immunoprecipitation on RSV infected cells coupled with mass spectrometry analysis. We identified 137 potential cellular partners of M2-1, among which many Proteins associated with mRNA metabolism, and particularly mRNA maturation, translation and stabilization. Among these, the cytoplasmic PolyA-Binding Protein 1 (PABPC1), a candidate with a major role in both translation and mRNA stabilization, was confirmed to interact with M2-1 using Protein complementation assay and specific immunoprecipitation. PABPC1 was also shown to colocalize with M2-1 from its accumulation in inclusion bodies associated granules (IBAGs) to its liberation in the cytoplasm. Altogether, these results strongly suggest that M2-1 interacts with viral mRNA and mRNA metabolism factors from transcription to translation, and imply that M2-1 may have an additional role in the fate of viral mRNA downstream of transcription. Human respiratory syncytial virus (RSV) is the most common cause of respiratory infection in neonates and infants worldwide. Globally, RSV is estimated to cause 33 million cases of acute respiratory illness in children under 5 years of age, resulting in 3.2 million hospital admissions and 118 200 child deaths a year, mostly in developing countries 1. Moreover, RSV infections in adults are increasingly associated with substantial morbidity and mortality in the elderly or at risk population, such as asthmatic and immunocompromised patients 2. RSV belongs to the pneumoviridae family of the Mononegavirales order 3. Its genome consists of a single-strand negative-sense RNA tightly encapsidated by the nucleoProtein N 4. Viral transcription and replication occur in the cytoplasm of infected cells, in virally induced cytoplasmic inclusions called inclusion bodies (IBs) 5-7. Replication is achieved by the viral RNA dependent RNA polymerase L and its cofactor the phosphoProtein P 8. Viral transcription requires an additional viral Protein, M2-1 9. The complex formed by L, P and M2-1 proceeds to the sequential transcription of RSV genes by a start and stop mechanism, producing capped and polyadenylated viral mRNAs 8. M2-1 ensures the polymerase processivity both intra-and inter-genically, preventing the synthesis of shortened mRNA and enabling transcription of downstream genes 9-11. M2-1 is composed of four 194 amino acid chains forming a stable homo-tetrameric Protein 12,13. Each M2-1 monomer encompasses a zinc finger domain (aa 7-25) at the N terminal extremity, an α helical oligomerization domain (aa 32-49) and a large globular core

  • The Interactome analysis of the Respiratory Syncytial Virus Protein M2-1 suggests a new role in viral mRNA metabolism post-transcription
    Scientific Reports, 2019
    Co-Authors: Camille Bouillier, Aurore Desquesnes, Sabine Blouquit-laye, Gina Cosentino, Thibaut Léger, Jean-françois Eleouet, Charles-adrien Richard, Vincent Rincheval, Delphine Sitterlin, Elyanne Gault
    Abstract:

    Human respiratory syncytial virus (RSV) is a globally prevalent negative-stranded RNA virus, which can cause life-threatening respiratory infections in young children, elderly people and immunocompromised patients. Its transcription termination factor M2-1 plays an essential role in viral transcription, but the mechanisms underpinning its function are still unclear. We investigated the cellular interactome of M2-1 using green fluorescent Protein (GFP)-trap immunoprecipitation on RSV infected cells coupled with mass spectrometry analysis. We identified 137 potential cellular partners of M2-1, among which many Proteins associated with mRNA metabolism, and particularly mRNA maturation, translation and stabilization. Among these, the cytoplasmic PolyA-Binding Protein 1 (PABPC1), a candidate with a major role in both translation and mRNA stabilization, was confirmed to interact with M2-1 using Protein complementation assay and specific immunoprecipitation. PABPC1 was also shown to colocalize with M2-1 from its accumulation in inclusion bodies associated granules (IBAGs) to its liberation in the cytoplasm. Altogether, these results strongly suggest that M2-1 interacts with viral mRNA and mRNA metabolism factors from transcription to translation, and imply that M2-1 may have an additional role in the fate of viral mRNA downstream of transcription.

Camille Bouillier - One of the best experts on this subject based on the ideXlab platform.

  • The interactome analysis of the Respiratory Syncytial Virus Protein M2-1 suggests a new role in viral mRNA metabolism post- transcription
    Scientific Reports, 2019
    Co-Authors: Camille Bouillier, Aurore Desquesnes, Sabine Blouquit-laye, Gina Cosentino, Thibaut Léger, Jean-françois Eleouet, Charles-adrien Richard, Vincent Rincheval, Delphine Sitterlin, Elyanne Gault
    Abstract:

    Human respiratory syncytial virus (RSV) is a globally prevalent negative-stranded RNA virus, which can cause life-threatening respiratory infections in young children, elderly people and immunocompromised patients. Its transcription termination factor M2-1 plays an essential role in viral transcription, but the mechanisms underpinning its function are still unclear. We investigated the cellular interactome of M2-1 using green fluorescent Protein (GFP)-trap immunoprecipitation on RSV infected cells coupled with mass spectrometry analysis. We identified 137 potential cellular partners of M2-1, among which many Proteins associated with mRNA metabolism, and particularly mRNA maturation, translation and stabilization. Among these, the cytoplasmic PolyA-Binding Protein 1 (PABPC1), a candidate with a major role in both translation and mRNA stabilization, was confirmed to interact with M2-1 using Protein complementation assay and specific immunoprecipitation. PABPC1 was also shown to colocalize with M2-1 from its accumulation in inclusion bodies associated granules (IBAGs) to its liberation in the cytoplasm. Altogether, these results strongly suggest that M2-1 interacts with viral mRNA and mRNA metabolism factors from transcription to translation, and imply that M2-1 may have an additional role in the fate of viral mRNA downstream of transcription. Human respiratory syncytial virus (RSV) is the most common cause of respiratory infection in neonates and infants worldwide. Globally, RSV is estimated to cause 33 million cases of acute respiratory illness in children under 5 years of age, resulting in 3.2 million hospital admissions and 118 200 child deaths a year, mostly in developing countries 1. Moreover, RSV infections in adults are increasingly associated with substantial morbidity and mortality in the elderly or at risk population, such as asthmatic and immunocompromised patients 2. RSV belongs to the pneumoviridae family of the Mononegavirales order 3. Its genome consists of a single-strand negative-sense RNA tightly encapsidated by the nucleoProtein N 4. Viral transcription and replication occur in the cytoplasm of infected cells, in virally induced cytoplasmic inclusions called inclusion bodies (IBs) 5-7. Replication is achieved by the viral RNA dependent RNA polymerase L and its cofactor the phosphoProtein P 8. Viral transcription requires an additional viral Protein, M2-1 9. The complex formed by L, P and M2-1 proceeds to the sequential transcription of RSV genes by a start and stop mechanism, producing capped and polyadenylated viral mRNAs 8. M2-1 ensures the polymerase processivity both intra-and inter-genically, preventing the synthesis of shortened mRNA and enabling transcription of downstream genes 9-11. M2-1 is composed of four 194 amino acid chains forming a stable homo-tetrameric Protein 12,13. Each M2-1 monomer encompasses a zinc finger domain (aa 7-25) at the N terminal extremity, an α helical oligomerization domain (aa 32-49) and a large globular core

  • The Interactome analysis of the Respiratory Syncytial Virus Protein M2-1 suggests a new role in viral mRNA metabolism post-transcription
    Scientific Reports, 2019
    Co-Authors: Camille Bouillier, Aurore Desquesnes, Sabine Blouquit-laye, Gina Cosentino, Thibaut Léger, Jean-françois Eleouet, Charles-adrien Richard, Vincent Rincheval, Delphine Sitterlin, Elyanne Gault
    Abstract:

    Human respiratory syncytial virus (RSV) is a globally prevalent negative-stranded RNA virus, which can cause life-threatening respiratory infections in young children, elderly people and immunocompromised patients. Its transcription termination factor M2-1 plays an essential role in viral transcription, but the mechanisms underpinning its function are still unclear. We investigated the cellular interactome of M2-1 using green fluorescent Protein (GFP)-trap immunoprecipitation on RSV infected cells coupled with mass spectrometry analysis. We identified 137 potential cellular partners of M2-1, among which many Proteins associated with mRNA metabolism, and particularly mRNA maturation, translation and stabilization. Among these, the cytoplasmic PolyA-Binding Protein 1 (PABPC1), a candidate with a major role in both translation and mRNA stabilization, was confirmed to interact with M2-1 using Protein complementation assay and specific immunoprecipitation. PABPC1 was also shown to colocalize with M2-1 from its accumulation in inclusion bodies associated granules (IBAGs) to its liberation in the cytoplasm. Altogether, these results strongly suggest that M2-1 interacts with viral mRNA and mRNA metabolism factors from transcription to translation, and imply that M2-1 may have an additional role in the fate of viral mRNA downstream of transcription.

  • L'analyse de l'interactome du facteur de transcription M2-1 du Virus Respiratoire Syncytial révèle une interaction avec PABPC1 (PolyA-Binding Protein cytoplasmic 1)
    2019
    Co-Authors: Camille Bouillier
    Abstract:

    Bien que le Virus Respiratoire Syncytial, responsable de la bronchiolite du nourrisson, soit aujourd’hui un problème de santé publique majeur, il n’existe encore aucun vaccin ou antiviral curatif contre ce pathogène. Le manque de données sur les étapes clés du cycle viral et sur les interactions virus-cellule freine le développement de nouvelles molécules antivirales.Nous avons étudié l’interactome de deux protéines virales : la polymérase L et le facteur de transcription M2-1. Dans ce but, nous avons mis au point un crible s’appuyant à la fois sur des critères d’interactomique et sur des critères fonctionnels.La première étape consistait à identifier des partenaires potentiels de M2-1 et L par des co-immunoprécipitations couplées à une approche de protéomique quantitative. Pour plus de pertinence, ce crible a été réalisé sur cellules infectées, grâce des virus recombinants produits par génétique inverse. Ceci nous a permis d’identifier 45 et 137 partenaires potentiels de L et M2-1 respectivement. Une étude systématique de l’impact de l’inhibition de 15 partenaires potentiels de M2-1 sur la multiplication virale a mis en avant trois candidats : ILF2, PABPN1 et PABPC1.Nous nous sommes par la suite concentrés sur PABPC1. L’inhibition de l’expression de PABPC1 altère la multiplication virale, mais nous n’avons pas pu mettre en évidence un effet spécifique sur la transcription ou la traduction virale. Son interaction avec M2-1 a été confirmée, et le domaine MLLE de PABPC1 a été identifié comme le site de liaison à M2-1. L’interaction entre M2-1 et PABPC1 a été observée à la fois dans le cytoplasme et dans les IBAGs, des sous-structures concentrant les ARNm viraux au sein des corps d’inclusion viraux. Nous avons formulé l’hypothèse que M2-1, liée à PABPC1, accompagne les ARNm viraux après leur sortie des corps d’inclusion. Ceci suggère un rôle de M2-1 dans le devenir des ARNm viraux en aval de leur transcription.

  • l analyse de l interactome du facteur de transcription m2 1 du virus respiratoire syncytial revele une interaction avec pabpc1 polya binding Protein cytoplasmic 1
    2019
    Co-Authors: Camille Bouillier
    Abstract:

    Bien que le Virus Respiratoire Syncytial, responsable de la bronchiolite du nourrisson, soit aujourd’hui un probleme de sante publique majeur, il n’existe encore aucun vaccin ou antiviral curatif contre ce pathogene. Le manque de donnees sur les etapes cles du cycle viral et sur les interactions virus-cellule freine le developpement de nouvelles molecules antivirales.Nous avons etudie l’interactome de deux Proteines virales : la polymerase L et le facteur de transcription M2-1. Dans ce but, nous avons mis au point un crible s’appuyant a la fois sur des criteres d’interactomique et sur des criteres fonctionnels.La premiere etape consistait a identifier des partenaires potentiels de M2-1 et L par des co-immunoprecipitations couplees a une approche de proteomique quantitative. Pour plus de pertinence, ce crible a ete realise sur cellules infectees, grâce des virus recombinants produits par genetique inverse. Ceci nous a permis d’identifier 45 et 137 partenaires potentiels de L et M2-1 respectivement. Une etude systematique de l’impact de l’inhibition de 15 partenaires potentiels de M2-1 sur la multiplication virale a mis en avant trois candidats : ILF2, PABPN1 et PABPC1.Nous nous sommes par la suite concentres sur PABPC1. L’inhibition de l’expression de PABPC1 altere la multiplication virale, mais nous n’avons pas pu mettre en evidence un effet specifique sur la transcription ou la traduction virale. Son interaction avec M2-1 a ete confirmee, et le domaine MLLE de PABPC1 a ete identifie comme le site de liaison a M2-1. L’interaction entre M2-1 et PABPC1 a ete observee a la fois dans le cytoplasme et dans les IBAGs, des sous-structures concentrant les ARNm viraux au sein des corps d’inclusion viraux. Nous avons formule l’hypothese que M2-1, liee a PABPC1, accompagne les ARNm viraux apres leur sortie des corps d’inclusion. Ceci suggere un role de M2-1 dans le devenir des ARNm viraux en aval de leur transcription.

Vincent Rincheval - One of the best experts on this subject based on the ideXlab platform.

  • The interactome analysis of the Respiratory Syncytial Virus Protein M2-1 suggests a new role in viral mRNA metabolism post- transcription
    Scientific Reports, 2019
    Co-Authors: Camille Bouillier, Aurore Desquesnes, Sabine Blouquit-laye, Gina Cosentino, Thibaut Léger, Jean-françois Eleouet, Charles-adrien Richard, Vincent Rincheval, Delphine Sitterlin, Elyanne Gault
    Abstract:

    Human respiratory syncytial virus (RSV) is a globally prevalent negative-stranded RNA virus, which can cause life-threatening respiratory infections in young children, elderly people and immunocompromised patients. Its transcription termination factor M2-1 plays an essential role in viral transcription, but the mechanisms underpinning its function are still unclear. We investigated the cellular interactome of M2-1 using green fluorescent Protein (GFP)-trap immunoprecipitation on RSV infected cells coupled with mass spectrometry analysis. We identified 137 potential cellular partners of M2-1, among which many Proteins associated with mRNA metabolism, and particularly mRNA maturation, translation and stabilization. Among these, the cytoplasmic PolyA-Binding Protein 1 (PABPC1), a candidate with a major role in both translation and mRNA stabilization, was confirmed to interact with M2-1 using Protein complementation assay and specific immunoprecipitation. PABPC1 was also shown to colocalize with M2-1 from its accumulation in inclusion bodies associated granules (IBAGs) to its liberation in the cytoplasm. Altogether, these results strongly suggest that M2-1 interacts with viral mRNA and mRNA metabolism factors from transcription to translation, and imply that M2-1 may have an additional role in the fate of viral mRNA downstream of transcription. Human respiratory syncytial virus (RSV) is the most common cause of respiratory infection in neonates and infants worldwide. Globally, RSV is estimated to cause 33 million cases of acute respiratory illness in children under 5 years of age, resulting in 3.2 million hospital admissions and 118 200 child deaths a year, mostly in developing countries 1. Moreover, RSV infections in adults are increasingly associated with substantial morbidity and mortality in the elderly or at risk population, such as asthmatic and immunocompromised patients 2. RSV belongs to the pneumoviridae family of the Mononegavirales order 3. Its genome consists of a single-strand negative-sense RNA tightly encapsidated by the nucleoProtein N 4. Viral transcription and replication occur in the cytoplasm of infected cells, in virally induced cytoplasmic inclusions called inclusion bodies (IBs) 5-7. Replication is achieved by the viral RNA dependent RNA polymerase L and its cofactor the phosphoProtein P 8. Viral transcription requires an additional viral Protein, M2-1 9. The complex formed by L, P and M2-1 proceeds to the sequential transcription of RSV genes by a start and stop mechanism, producing capped and polyadenylated viral mRNAs 8. M2-1 ensures the polymerase processivity both intra-and inter-genically, preventing the synthesis of shortened mRNA and enabling transcription of downstream genes 9-11. M2-1 is composed of four 194 amino acid chains forming a stable homo-tetrameric Protein 12,13. Each M2-1 monomer encompasses a zinc finger domain (aa 7-25) at the N terminal extremity, an α helical oligomerization domain (aa 32-49) and a large globular core

  • The Interactome analysis of the Respiratory Syncytial Virus Protein M2-1 suggests a new role in viral mRNA metabolism post-transcription
    Scientific Reports, 2019
    Co-Authors: Camille Bouillier, Aurore Desquesnes, Sabine Blouquit-laye, Gina Cosentino, Thibaut Léger, Jean-françois Eleouet, Charles-adrien Richard, Vincent Rincheval, Delphine Sitterlin, Elyanne Gault
    Abstract:

    Human respiratory syncytial virus (RSV) is a globally prevalent negative-stranded RNA virus, which can cause life-threatening respiratory infections in young children, elderly people and immunocompromised patients. Its transcription termination factor M2-1 plays an essential role in viral transcription, but the mechanisms underpinning its function are still unclear. We investigated the cellular interactome of M2-1 using green fluorescent Protein (GFP)-trap immunoprecipitation on RSV infected cells coupled with mass spectrometry analysis. We identified 137 potential cellular partners of M2-1, among which many Proteins associated with mRNA metabolism, and particularly mRNA maturation, translation and stabilization. Among these, the cytoplasmic PolyA-Binding Protein 1 (PABPC1), a candidate with a major role in both translation and mRNA stabilization, was confirmed to interact with M2-1 using Protein complementation assay and specific immunoprecipitation. PABPC1 was also shown to colocalize with M2-1 from its accumulation in inclusion bodies associated granules (IBAGs) to its liberation in the cytoplasm. Altogether, these results strongly suggest that M2-1 interacts with viral mRNA and mRNA metabolism factors from transcription to translation, and imply that M2-1 may have an additional role in the fate of viral mRNA downstream of transcription.

Charles-adrien Richard - One of the best experts on this subject based on the ideXlab platform.

  • The interactome analysis of the Respiratory Syncytial Virus Protein M2-1 suggests a new role in viral mRNA metabolism post- transcription
    Scientific Reports, 2019
    Co-Authors: Camille Bouillier, Aurore Desquesnes, Sabine Blouquit-laye, Gina Cosentino, Thibaut Léger, Jean-françois Eleouet, Charles-adrien Richard, Vincent Rincheval, Delphine Sitterlin, Elyanne Gault
    Abstract:

    Human respiratory syncytial virus (RSV) is a globally prevalent negative-stranded RNA virus, which can cause life-threatening respiratory infections in young children, elderly people and immunocompromised patients. Its transcription termination factor M2-1 plays an essential role in viral transcription, but the mechanisms underpinning its function are still unclear. We investigated the cellular interactome of M2-1 using green fluorescent Protein (GFP)-trap immunoprecipitation on RSV infected cells coupled with mass spectrometry analysis. We identified 137 potential cellular partners of M2-1, among which many Proteins associated with mRNA metabolism, and particularly mRNA maturation, translation and stabilization. Among these, the cytoplasmic PolyA-Binding Protein 1 (PABPC1), a candidate with a major role in both translation and mRNA stabilization, was confirmed to interact with M2-1 using Protein complementation assay and specific immunoprecipitation. PABPC1 was also shown to colocalize with M2-1 from its accumulation in inclusion bodies associated granules (IBAGs) to its liberation in the cytoplasm. Altogether, these results strongly suggest that M2-1 interacts with viral mRNA and mRNA metabolism factors from transcription to translation, and imply that M2-1 may have an additional role in the fate of viral mRNA downstream of transcription. Human respiratory syncytial virus (RSV) is the most common cause of respiratory infection in neonates and infants worldwide. Globally, RSV is estimated to cause 33 million cases of acute respiratory illness in children under 5 years of age, resulting in 3.2 million hospital admissions and 118 200 child deaths a year, mostly in developing countries 1. Moreover, RSV infections in adults are increasingly associated with substantial morbidity and mortality in the elderly or at risk population, such as asthmatic and immunocompromised patients 2. RSV belongs to the pneumoviridae family of the Mononegavirales order 3. Its genome consists of a single-strand negative-sense RNA tightly encapsidated by the nucleoProtein N 4. Viral transcription and replication occur in the cytoplasm of infected cells, in virally induced cytoplasmic inclusions called inclusion bodies (IBs) 5-7. Replication is achieved by the viral RNA dependent RNA polymerase L and its cofactor the phosphoProtein P 8. Viral transcription requires an additional viral Protein, M2-1 9. The complex formed by L, P and M2-1 proceeds to the sequential transcription of RSV genes by a start and stop mechanism, producing capped and polyadenylated viral mRNAs 8. M2-1 ensures the polymerase processivity both intra-and inter-genically, preventing the synthesis of shortened mRNA and enabling transcription of downstream genes 9-11. M2-1 is composed of four 194 amino acid chains forming a stable homo-tetrameric Protein 12,13. Each M2-1 monomer encompasses a zinc finger domain (aa 7-25) at the N terminal extremity, an α helical oligomerization domain (aa 32-49) and a large globular core

  • The Interactome analysis of the Respiratory Syncytial Virus Protein M2-1 suggests a new role in viral mRNA metabolism post-transcription
    Scientific Reports, 2019
    Co-Authors: Camille Bouillier, Aurore Desquesnes, Sabine Blouquit-laye, Gina Cosentino, Thibaut Léger, Jean-françois Eleouet, Charles-adrien Richard, Vincent Rincheval, Delphine Sitterlin, Elyanne Gault
    Abstract:

    Human respiratory syncytial virus (RSV) is a globally prevalent negative-stranded RNA virus, which can cause life-threatening respiratory infections in young children, elderly people and immunocompromised patients. Its transcription termination factor M2-1 plays an essential role in viral transcription, but the mechanisms underpinning its function are still unclear. We investigated the cellular interactome of M2-1 using green fluorescent Protein (GFP)-trap immunoprecipitation on RSV infected cells coupled with mass spectrometry analysis. We identified 137 potential cellular partners of M2-1, among which many Proteins associated with mRNA metabolism, and particularly mRNA maturation, translation and stabilization. Among these, the cytoplasmic PolyA-Binding Protein 1 (PABPC1), a candidate with a major role in both translation and mRNA stabilization, was confirmed to interact with M2-1 using Protein complementation assay and specific immunoprecipitation. PABPC1 was also shown to colocalize with M2-1 from its accumulation in inclusion bodies associated granules (IBAGs) to its liberation in the cytoplasm. Altogether, these results strongly suggest that M2-1 interacts with viral mRNA and mRNA metabolism factors from transcription to translation, and imply that M2-1 may have an additional role in the fate of viral mRNA downstream of transcription.

Aurore Desquesnes - One of the best experts on this subject based on the ideXlab platform.

  • The interactome analysis of the Respiratory Syncytial Virus Protein M2-1 suggests a new role in viral mRNA metabolism post- transcription
    Scientific Reports, 2019
    Co-Authors: Camille Bouillier, Aurore Desquesnes, Sabine Blouquit-laye, Gina Cosentino, Thibaut Léger, Jean-françois Eleouet, Charles-adrien Richard, Vincent Rincheval, Delphine Sitterlin, Elyanne Gault
    Abstract:

    Human respiratory syncytial virus (RSV) is a globally prevalent negative-stranded RNA virus, which can cause life-threatening respiratory infections in young children, elderly people and immunocompromised patients. Its transcription termination factor M2-1 plays an essential role in viral transcription, but the mechanisms underpinning its function are still unclear. We investigated the cellular interactome of M2-1 using green fluorescent Protein (GFP)-trap immunoprecipitation on RSV infected cells coupled with mass spectrometry analysis. We identified 137 potential cellular partners of M2-1, among which many Proteins associated with mRNA metabolism, and particularly mRNA maturation, translation and stabilization. Among these, the cytoplasmic PolyA-Binding Protein 1 (PABPC1), a candidate with a major role in both translation and mRNA stabilization, was confirmed to interact with M2-1 using Protein complementation assay and specific immunoprecipitation. PABPC1 was also shown to colocalize with M2-1 from its accumulation in inclusion bodies associated granules (IBAGs) to its liberation in the cytoplasm. Altogether, these results strongly suggest that M2-1 interacts with viral mRNA and mRNA metabolism factors from transcription to translation, and imply that M2-1 may have an additional role in the fate of viral mRNA downstream of transcription. Human respiratory syncytial virus (RSV) is the most common cause of respiratory infection in neonates and infants worldwide. Globally, RSV is estimated to cause 33 million cases of acute respiratory illness in children under 5 years of age, resulting in 3.2 million hospital admissions and 118 200 child deaths a year, mostly in developing countries 1. Moreover, RSV infections in adults are increasingly associated with substantial morbidity and mortality in the elderly or at risk population, such as asthmatic and immunocompromised patients 2. RSV belongs to the pneumoviridae family of the Mononegavirales order 3. Its genome consists of a single-strand negative-sense RNA tightly encapsidated by the nucleoProtein N 4. Viral transcription and replication occur in the cytoplasm of infected cells, in virally induced cytoplasmic inclusions called inclusion bodies (IBs) 5-7. Replication is achieved by the viral RNA dependent RNA polymerase L and its cofactor the phosphoProtein P 8. Viral transcription requires an additional viral Protein, M2-1 9. The complex formed by L, P and M2-1 proceeds to the sequential transcription of RSV genes by a start and stop mechanism, producing capped and polyadenylated viral mRNAs 8. M2-1 ensures the polymerase processivity both intra-and inter-genically, preventing the synthesis of shortened mRNA and enabling transcription of downstream genes 9-11. M2-1 is composed of four 194 amino acid chains forming a stable homo-tetrameric Protein 12,13. Each M2-1 monomer encompasses a zinc finger domain (aa 7-25) at the N terminal extremity, an α helical oligomerization domain (aa 32-49) and a large globular core

  • The Interactome analysis of the Respiratory Syncytial Virus Protein M2-1 suggests a new role in viral mRNA metabolism post-transcription
    Scientific Reports, 2019
    Co-Authors: Camille Bouillier, Aurore Desquesnes, Sabine Blouquit-laye, Gina Cosentino, Thibaut Léger, Jean-françois Eleouet, Charles-adrien Richard, Vincent Rincheval, Delphine Sitterlin, Elyanne Gault
    Abstract:

    Human respiratory syncytial virus (RSV) is a globally prevalent negative-stranded RNA virus, which can cause life-threatening respiratory infections in young children, elderly people and immunocompromised patients. Its transcription termination factor M2-1 plays an essential role in viral transcription, but the mechanisms underpinning its function are still unclear. We investigated the cellular interactome of M2-1 using green fluorescent Protein (GFP)-trap immunoprecipitation on RSV infected cells coupled with mass spectrometry analysis. We identified 137 potential cellular partners of M2-1, among which many Proteins associated with mRNA metabolism, and particularly mRNA maturation, translation and stabilization. Among these, the cytoplasmic PolyA-Binding Protein 1 (PABPC1), a candidate with a major role in both translation and mRNA stabilization, was confirmed to interact with M2-1 using Protein complementation assay and specific immunoprecipitation. PABPC1 was also shown to colocalize with M2-1 from its accumulation in inclusion bodies associated granules (IBAGs) to its liberation in the cytoplasm. Altogether, these results strongly suggest that M2-1 interacts with viral mRNA and mRNA metabolism factors from transcription to translation, and imply that M2-1 may have an additional role in the fate of viral mRNA downstream of transcription.