Publications
2021
Scheer Hélène, Almeida Caroline, Ferrier Emilie, Simonnot Quentin, Poirier Laure, Pflieger David, Sement François M., Koechler Sandrine, Piermaria Christina, Krawczyk Paweł, Mroczek Seweryn, Chicher Johana, Kuhn Lauriane, Dziembowski Andrzej, Hammann Philippe, Zuber Hélène, Gagliardi Dominique
The TUTase URT1 connects decapping activators and prevents the accumulation of excessively deadenylated mRNAs to avoid siRNA biogenesis Article de journal
Dans: Nature Communications, vol. 12, no. 1, p. 1298, 2021, ISSN: 2041-1723.
Résumé | Liens | BibTeX | Étiquettes: Arabidopsis, Arabidopsis Proteins, Co-Repressor Proteins, DEAD-box RNA Helicases, Gene Expression Regulation, Humans, messenger, Plant, PPSE, Proto-Oncogene Proteins, Ribonucleoproteins, RNA, RNA Nucleotidyltransferases, RNA Stability, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Small Interfering, Tobacco, transcriptome, Uridine
@article{scheer_tutase_2021,
title = {The TUTase URT1 connects decapping activators and prevents the accumulation of excessively deadenylated mRNAs to avoid siRNA biogenesis},
author = {Hélène Scheer and Caroline Almeida and Emilie Ferrier and Quentin Simonnot and Laure Poirier and David Pflieger and François M. Sement and Sandrine Koechler and Christina Piermaria and Paweł Krawczyk and Seweryn Mroczek and Johana Chicher and Lauriane Kuhn and Andrzej Dziembowski and Philippe Hammann and Hélène Zuber and Dominique Gagliardi},
doi = {10.1038/s41467-021-21382-2},
issn = {2041-1723},
year = {2021},
date = {2021-02-01},
journal = {Nature Communications},
volume = {12},
number = {1},
pages = {1298},
abstract = {Uridylation is a widespread modification destabilizing eukaryotic mRNAs. Yet, molecular mechanisms underlying TUTase-mediated mRNA degradation remain mostly unresolved. Here, we report that the Arabidopsis TUTase URT1 participates in a molecular network connecting several translational repressors/decapping activators. URT1 directly interacts with DECAPPING 5 (DCP5), the Arabidopsis ortholog of human LSM14 and yeast Scd6, and this interaction connects URT1 to additional decay factors like DDX6/Dhh1-like RNA helicases. Nanopore direct RNA sequencing reveals a global role of URT1 in shaping poly(A) tail length, notably by preventing the accumulation of excessively deadenylated mRNAs. Based on in vitro and in planta data, we propose a model that explains how URT1 could reduce the accumulation of oligo(A)-tailed mRNAs both by favoring their degradation and because 3' terminal uridines intrinsically hinder deadenylation. Importantly, preventing the accumulation of excessively deadenylated mRNAs avoids the biogenesis of illegitimate siRNAs that silence endogenous mRNAs and perturb Arabidopsis growth and development.},
keywords = {Arabidopsis, Arabidopsis Proteins, Co-Repressor Proteins, DEAD-box RNA Helicases, Gene Expression Regulation, Humans, messenger, Plant, PPSE, Proto-Oncogene Proteins, Ribonucleoproteins, RNA, RNA Nucleotidyltransferases, RNA Stability, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Small Interfering, Tobacco, transcriptome, Uridine},
pubstate = {published},
tppubtype = {article}
}
Méteignier Louis-Valentin, Ghandour Rabea, Zimmerman Aude, Kuhn Lauriane, Meurer Jörg, Zoschke Reimo, Hammani Kamel
Arabidopsis mTERF9 protein promotes chloroplast ribosomal assembly and translation by establishing ribonucleoprotein interactions in vivo Article de journal
Dans: Nucleic Acids Research, vol. 49, no. 2, p. 1114–1132, 2021, ISSN: 1362-4962.
Résumé | Liens | BibTeX | Étiquettes: 16S, 23S, Arabidopsis, Arabidopsis Proteins, Chloroplast Proteins, Chloroplasts, Gene Expression Regulation, Organelle Biogenesis, Peptide Termination Factors, Plant, Polyribosomes, PPSE, Protein Biosynthesis, Recombinant Proteins, Ribonucleoproteins, Ribosomal, ribosomes, RNA, Substrate Specificity
@article{meteignier_arabidopsis_2021,
title = {Arabidopsis mTERF9 protein promotes chloroplast ribosomal assembly and translation by establishing ribonucleoprotein interactions in vivo},
author = {Louis-Valentin Méteignier and Rabea Ghandour and Aude Zimmerman and Lauriane Kuhn and Jörg Meurer and Reimo Zoschke and Kamel Hammani},
doi = {10.1093/nar/gkaa1244},
issn = {1362-4962},
year = {2021},
date = {2021-01-01},
journal = {Nucleic Acids Research},
volume = {49},
number = {2},
pages = {1114--1132},
abstract = {The mitochondrial transcription termination factor proteins are nuclear-encoded nucleic acid binders defined by degenerate tandem helical-repeats of ∼30 amino acids. They are found in metazoans and plants where they localize in organelles. In higher plants, the mTERF family comprises ∼30 members and several of these have been linked to plant development and response to abiotic stress. However, knowledge of the molecular basis underlying these physiological effects is scarce. We show that the Arabidopsis mTERF9 protein promotes the accumulation of the 16S and 23S rRNAs in chloroplasts, and interacts predominantly with the 16S rRNA in vivo and in vitro. Furthermore, mTERF9 is found in large complexes containing ribosomes and polysomes in chloroplasts. The comprehensive analysis of mTERF9 in vivo protein interactome identified many subunits of the 70S ribosome whose assembly is compromised in the null mterf9 mutant, putative ribosome biogenesis factors and CPN60 chaperonins. Protein interaction assays in yeast revealed that mTERF9 directly interact with these proteins. Our data demonstrate that mTERF9 integrates protein-protein and protein-RNA interactions to promote chloroplast ribosomal assembly and translation. Besides extending our knowledge of mTERF functional repertoire in plants, these findings provide an important insight into the chloroplast ribosome biogenesis.},
keywords = {16S, 23S, Arabidopsis, Arabidopsis Proteins, Chloroplast Proteins, Chloroplasts, Gene Expression Regulation, Organelle Biogenesis, Peptide Termination Factors, Plant, Polyribosomes, PPSE, Protein Biosynthesis, Recombinant Proteins, Ribonucleoproteins, Ribosomal, ribosomes, RNA, Substrate Specificity},
pubstate = {published},
tppubtype = {article}
}
2007
Monneaux Fanny, Parietti Véronique, Briand Jean-Paul, Muller Sylviane
Importance of spliceosomal RNP1 motif for intermolecular Ŧ-B cell spreading and tolerance restoration in lupus Article de journal
Dans: Arthritis Research & Therapy, vol. 9, no. 5, p. R111, 2007, ISSN: 1478-6362.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Motifs, Amino Acid Sequence, Animals, B-Lymphocytes, I2CT, Immune Tolerance, Inbred MRL lpr, Lupus Erythematosus, Mice, Molecular Sequence Data, Monneaux, Ribonucleoproteins, RNA-Binding Proteins, Saccharomyces cerevisiae Proteins, Spliceosomes, Systemic, T-Lymphocytes, Team-Dumortier
@article{monneaux_importance_2007,
title = {Importance of spliceosomal RNP1 motif for intermolecular Ŧ-B cell spreading and tolerance restoration in lupus},
author = {Fanny Monneaux and Véronique Parietti and Jean-Paul Briand and Sylviane Muller},
doi = {10.1186/ar2317},
issn = {1478-6362},
year = {2007},
date = {2007-01-01},
journal = {Arthritis Research & Therapy},
volume = {9},
number = {5},
pages = {R111},
abstract = {We previously demonstrated the importance of the RNP1 motif-bearing region 131-151 of the U1-70K spliceosomal protein in the intramolecular T-B spreading that occurs in MRL/lpr lupus mice. Here, we analyze the involvement of RNP1 motif in the development and prevention of naturally-occurring intermolecular T-B cell diversification. We found that MRL/lpr peripheral blood lymphocytes proliferated in response to peptides containing or corresponding exactly to the RNP1 motif of spliceosomal U1-70K, U1-A and hnRNP-A2 proteins. We also demonstrated that rabbit antibodies to peptide 131-151 cross-reacted with U1-70K, U1-A and hnRNP-A2 RNP1-peptides. These antibodies recognized the U1-70K and U1-A proteins, and also U1-C and SmD1 proteins, which are devoid of RNP1 motif. Repeated administration of phosphorylated peptide P140 into MRL/lpr mice abolished T-cell response to several peptides from the U1-70K, U1-A and SmD1 proteins without affecting antibody and T-cell responses to foreign (viral) antigen in treated mice challenged with infectious virus. These results emphasized the importance of the dominant RNP1 region, which seems to be central in the activation cascade of B and T cells reacting with spliceosomal RNP1+ and RNP1- spliceosomal proteins. The tolerogenic peptide P140, which is recognized by lupus patients' CD4+ T cells and known to protect MRL/lpr mice, is able to thwart emergence of intermolecular T-cell spreading in treated animals.},
keywords = {Amino Acid Motifs, Amino Acid Sequence, Animals, B-Lymphocytes, I2CT, Immune Tolerance, Inbred MRL lpr, Lupus Erythematosus, Mice, Molecular Sequence Data, Monneaux, Ribonucleoproteins, RNA-Binding Proteins, Saccharomyces cerevisiae Proteins, Spliceosomes, Systemic, T-Lymphocytes, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
2001
Monneaux F, Muller S
Key sequences involved in the spreading of the systemic autoimmune response to spliceosomal proteins Article de journal
Dans: Scandinavian Journal of Immunology, vol. 54, no. 1-2, p. 45–54, 2001, ISSN: 0300-9475.
Résumé | Liens | BibTeX | Étiquettes: Animals, Autoantibodies, Autoimmune Diseases, Autoimmunity, B-Lymphocyte, Epitopes, Humans, I2CT, Mice, Monneaux, Ribonucleoproteins, Spliceosomes, Team-Dumortier
@article{monneaux_key_2001,
title = {Key sequences involved in the spreading of the systemic autoimmune response to spliceosomal proteins},
author = {F Monneaux and S Muller},
doi = {10.1046/j.1365-3083.2001.00942.x},
issn = {0300-9475},
year = {2001},
date = {2001-01-01},
journal = {Scandinavian Journal of Immunology},
volume = {54},
number = {1-2},
pages = {45--54},
abstract = {Immune spreading to multiple intracellular antigens is likely to be of primary importance in organ-specific and systemic autoimmune diseases. A number of mechanisms by which immune spreading may occur from only a single autoreactive epitope have been proposed. Search for an initiator or early epitope thus represents an important area of investigation. For example, many studies have focused on the identification of epitopes recognized by the antibodies from both patients with systemic lupus erythematosus (SLE) and lupus-prone mice. Recently, an autoepitope present in the 70K U1 ribonucleo protein (RNP) and recognized by CD4+ T cells from lupus mice has also been identified. Here, we analyze the results of B- and T-cell-epitope mapping studies of several RNPs present in the spliceosome and propose a model of epitope spreading. In this model, a consensus sequence (the RNP motif) conserved in many nuclear, nucleolar and cytoplasmic antigens, might play a role as 'driver' epitope. This hypothesis is based on the observation that this sequence is recognized by CD4+ T cells from lupus mice and is often targeted by autoantibodies, very early during the course of the disease. Targeting this region that is repeated in different self-antigens, might represent an interesting strategy to interfere with the continuous T-cell stimulation and exposure to specific antigens.},
keywords = {Animals, Autoantibodies, Autoimmune Diseases, Autoimmunity, B-Lymphocyte, Epitopes, Humans, I2CT, Mice, Monneaux, Ribonucleoproteins, Spliceosomes, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Monneaux F, Dumortier H, Steiner G, Briand J P, Muller S
Murine models of systemic lupus erythematosus: B and Ŧ cell responses to spliceosomal ribonucleoproteins in MRL/Fas(lpr) and (NZB x NZW)F(1) lupus mice Article de journal
Dans: International Immunology, vol. 13, no. 9, p. 1155–1163, 2001, ISSN: 0953-8178.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antibody Specificity, B-Lymphocytes, Crosses, Dumortier, fas Receptor, Female, Genetic, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Heterogeneous-Nuclear Ribonucleoproteins, Histocompatibility Antigens Class II, I2CT, Immunoglobulin G, Inbred MRL lpr, Inbred NZB, Lupus Erythematosus, Mice, Monneaux, Peptide Fragments, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Species Specificity, Spliceosomes, Systemic, T-Lymphocytes, Team-Dumortier, U1 Small Nuclear
@article{monneaux_murine_2001,
title = {Murine models of systemic lupus erythematosus: B and Ŧ cell responses to spliceosomal ribonucleoproteins in MRL/Fas(lpr) and (NZB x NZW)F(1) lupus mice},
author = {F Monneaux and H Dumortier and G Steiner and J P Briand and S Muller},
doi = {10.1093/intimm/13.9.1155},
issn = {0953-8178},
year = {2001},
date = {2001-01-01},
journal = {International Immunology},
volume = {13},
number = {9},
pages = {1155--1163},
abstract = {(NZB x NZW)F(1) and MRL/Fas(lpr) lupus mice present a similar phenotype with a spectrum of autoantibodies associated with very severe nephritis. It is thought, however, that in contrast to other lupus-prone mice such as MRL/Fas(lpr) mice, (NZB x NZW)F(1) mice do not generate autoantibodies to ribonucleoproteins (RNP) Sm/RNP. In this study, we demonstrate that contrary to previous reports, the autoimmune response directed against Sm/RNP antigens also occurs in NZB x NZW mice. CD4(+) T cells from unprimed 10-week-old NZB x NZW mice proliferate and secrete IL-2 in response to peptide 131-151 of the U1-70K protein, which is known to contain a T(h) epitope recognized by CD4(+) T cells from MRL/Fas(lpr) mice. Peptide 131-151, which was found to bind I-A(k) and I-E(k) class II MHC molecules, also bound both I-A(d) and I-E(d) molecules. This result led us to also re-evaluate longitudinally the anti-Sm/RNP antibody response in NZB x NZW mice. We found that 25-week-old mice do produce antibodies reacting with several small nuclear and heterogeneous nuclear (hn) RNP proteins, such as SmD1, U1-70K and hnRNP A2/B1 proteins. The fine specificity of these antibodies was studied with overlapping synthetic peptides. The same antigenically positive and negative peptides were characterized in MRL/Fas(lpr) and NZB x NZW mice in the three proteins. This new finding can help to understand the mechanisms involved in the development of the anti-Sm/RNP antibody response and, particularly, the role played by non-MHC genes in this autoimmune response.},
keywords = {Animals, Antibody Specificity, B-Lymphocytes, Crosses, Dumortier, fas Receptor, Female, Genetic, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Heterogeneous-Nuclear Ribonucleoproteins, Histocompatibility Antigens Class II, I2CT, Immunoglobulin G, Inbred MRL lpr, Inbred NZB, Lupus Erythematosus, Mice, Monneaux, Peptide Fragments, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Species Specificity, Spliceosomes, Systemic, T-Lymphocytes, Team-Dumortier, U1 Small Nuclear},
pubstate = {published},
tppubtype = {article}
}
2000
Monneaux F, Muller S
Laboratory protocols for the identification of Th cell epitopes on self-antigens in mice with systemic autoimmune diseases Article de journal
Dans: Journal of Immunological Methods, vol. 244, no. 1-2, p. 195–204, 2000, ISSN: 0022-1759.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antigen Presentation, Antigen-Presenting Cells, Autoantigens, B-Lymphocytes, Coculture Techniques, Epitopes, Female, Flow Cytometry, I2CT, Inbred MRL lpr, Inbred NZB, Lupus Erythematosus, Lymphocyte Activation, Mice, Monneaux, Ribonucleoproteins, Small Nuclear, Systemic, T-Lymphocyte, Team-Dumortier, Th1 Cells, Th2 Cells
@article{monneaux_laboratory_2000,
title = {Laboratory protocols for the identification of Th cell epitopes on self-antigens in mice with systemic autoimmune diseases},
author = {F Monneaux and S Muller},
doi = {10.1016/s0022-1759(00)00256-8},
issn = {0022-1759},
year = {2000},
date = {2000-10-01},
journal = {Journal of Immunological Methods},
volume = {244},
number = {1-2},
pages = {195--204},
abstract = {T cells play a critical role in both the immunological and clinical manifestations of systemic autoimmune diseases such as systemic lupus erythematosus (SLE). Although in normal mice multiple T cell epitopes have been characterized in several self-proteins, there is little information on the fine specificity of autoreactive T cells in lupus model mice and humans. In SLE-prone mice and humans, the only Th cell epitopes identified at the molecular level in self-antigens concern histones and nucleosomes, and the 70-kD U1-snRNP protein. T cell characterization in certain autoimmune mice such as MRL lpr/lpr and NZB/NZW mice has been largely impaired by their hyporesponsiveness in response to mitogen and minimal IL-2 secretion. In addition, MRL lpr/lpr mice also develop lymphadenopathy characterized by the progressive accumulation of functionally immature CD4(-) CD8(-) T cells. It is therefore important to optimize the methods used to measure T cell proliferation and cytokine production ex vivo in order to identify minimal activation in the presence of appropriate antigen. The protocol described in this article has been used for identifying in young MRL lpr/lpr and NZB/NZW mice a CD4(+) T cell epitope in the murine 70-kD U1-RNP protein.},
keywords = {Animals, Antigen Presentation, Antigen-Presenting Cells, Autoantigens, B-Lymphocytes, Coculture Techniques, Epitopes, Female, Flow Cytometry, I2CT, Inbred MRL lpr, Inbred NZB, Lupus Erythematosus, Lymphocyte Activation, Mice, Monneaux, Ribonucleoproteins, Small Nuclear, Systemic, T-Lymphocyte, Team-Dumortier, Th1 Cells, Th2 Cells},
pubstate = {published},
tppubtype = {article}
}
Dumortier H, Monneaux F, Jahn-Schmid B, Briand J P, Skriner K, Cohen P L, Smolen J S, Steiner G, Muller S
B and Ŧ cell responses to the spliceosomal heterogeneous nuclear ribonucleoproteins A2 and B1 in normal and lupus mice Article de journal
Dans: Journal of Immunology (Baltimore, Md.: 1950), vol. 165, no. 4, p. 2297–2305, 2000, ISSN: 0022-1767.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence, Animals, Autoantibodies, B-Lymphocytes, Dumortier, Epitope Mapping, Female, Heterogeneous Nuclear, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Heterogeneous-Nuclear Ribonucleoproteins, Humans, I2CT, Immunoglobulin G, Inbred BALB C, Inbred C57BL, Inbred CBA, Inbred MRL lpr, Injections, Lupus Nephritis, Lymphocyte Activation, Male, Mice, Molecular Sequence Data, Monneaux, Peptide Fragments, Recombinant Proteins, Ribonucleoproteins, RNA, Spliceosomes, Subcutaneous, T-Lymphocytes, Team-Dumortier, transgenic
@article{dumortier_b_2000,
title = {B and Ŧ cell responses to the spliceosomal heterogeneous nuclear ribonucleoproteins A2 and B1 in normal and lupus mice},
author = {H Dumortier and F Monneaux and B Jahn-Schmid and J P Briand and K Skriner and P L Cohen and J S Smolen and G Steiner and S Muller},
doi = {10.4049/jimmunol.165.4.2297},
issn = {0022-1767},
year = {2000},
date = {2000-08-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {165},
number = {4},
pages = {2297--2305},
abstract = {Autoantibodies directed against spliceosomal heterogeneous nuclear ribonucleoproteins (hnRNPs) are a typical feature of rheumatoid arthritis, systemic lupus erythematosus, and mixed-connective tissue disease. With the aim of investigating a potential pathogenic role of these Abs, we have studied the Ab response to A2/B1 hnRNPs in different murine models of lupus. The specificity of anti-A2/B1 Abs was tested with a series of 14 overlapping synthetic peptides covering the region 1-206 of A2 that contains most of the epitopes recognized by patients' Abs. A major epitope recognized very early during the course of the disease by Abs from most of MRL lpr/lpr mice but not from other lupus mice and from mice of different MHC haplotypes immunized against B1 was identified in residues 50-70. This peptide contains a highly conserved sequence RGFGFVTF also present in other hnRNPs and small nuclear ribonucleoproteins. Abs reacting with a second A2 epitope identified in residues 35-55 were detectable several weeks later, suggesting an intramolecular B cell epitope spreading during the course of the disease. We identified several T cell epitopes within the region 35-175 that generated an effective Th cell response with IL-2 and IFN-gamma secretion in nonautoimmune CBA/J mice sharing the same MHC haplotype H-2k as MRL/lpr mice. None of the peptides stimulated T cells primed in vivo with B1. Because Abs to peptide 50-70 were detected significantly earlier than Abs reacting with other A2 peptides and the protein itself, it is possible that within the protein, this segment contains residues playing an initiator role in the induction of the anti-A2/B1 and antispliceosome Ab response.},
keywords = {Amino Acid Sequence, Animals, Autoantibodies, B-Lymphocytes, Dumortier, Epitope Mapping, Female, Heterogeneous Nuclear, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Heterogeneous-Nuclear Ribonucleoproteins, Humans, I2CT, Immunoglobulin G, Inbred BALB C, Inbred C57BL, Inbred CBA, Inbred MRL lpr, Injections, Lupus Nephritis, Lymphocyte Activation, Male, Mice, Molecular Sequence Data, Monneaux, Peptide Fragments, Recombinant Proteins, Ribonucleoproteins, RNA, Spliceosomes, Subcutaneous, T-Lymphocytes, Team-Dumortier, transgenic},
pubstate = {published},
tppubtype = {article}
}
1999
Dumortier H, Abbal M, Fort M, Briand J P, Cantagrel A, Muller S
MHC class II gene associations with autoantibodies to U1A and SmD1 proteins Article de journal
Dans: International Immunology, vol. 11, no. 2, p. 249–257, 1999, ISSN: 0953-8178.
Résumé | Liens | BibTeX | Étiquettes: Alleles, Antibody Specificity, Autoantibodies, Autoantigens, Autoimmune Diseases, Blotting, Dumortier, Enzyme-Linked Immunosorbent Assay, Genes, HLA-DP Antigens, HLA-DP beta-Chains, HLA-DQ Antigens, HLA-DQ beta-Chains, HLA-DR Antigens, HLA-DRB1 Chains, Humans, I2CT, MHC Class II, Peptides, Rheumatic Diseases, Ribonucleoprotein, Ribonucleoproteins, RNA-Binding Proteins, Small Nuclear, snRNP Core Proteins, Team-Dumortier, U1 Small Nuclear, Western
@article{dumortier_mhc_1999,
title = {MHC class II gene associations with autoantibodies to U1A and SmD1 proteins},
author = {H Dumortier and M Abbal and M Fort and J P Briand and A Cantagrel and S Muller},
doi = {10.1093/intimm/11.2.249},
issn = {0953-8178},
year = {1999},
date = {1999-01-01},
journal = {International Immunology},
volume = {11},
number = {2},
pages = {249--257},
abstract = {Autoantibodies against U small nuclear ribonucleoproteins (snRNP) are frequently present in the serum of patients with systemic rheumatic diseases, and have been reported to be associated with HLA-DR and -DQ genes. To better define the role of HLA genes in the production of such antibodies, we studied immunogenetic associations with autoantibodies reacting with U1 RNP, U1A and SmD1 proteins, and synthetic peptides containing immunodominant linear epitopes of these proteins. Only two out of the 15 overlapping peptides of U1A (i.e. peptides 35-58 and 257-282) and three of 11 peptides of SmD1 (i.e. peptides 1-20, 44-67 and 97-119) were significantly recognized by patients' sera selected on the basis of their antibody positivity with RNP in immunodiffusion. The distribution of DRB1, DQB1 and DPB1 alleles among the anti-RNP antibody-positive patients (n = 28) and healthy control subjects was similar. Antibodies against U1A (tested in Western immunoblotting with HeLa cell extracts) were positively associated to DRB1*06 allele; antibodies reacting with SmD1 peptide 44-67 were negatively associated to DRB1*02 and DQB1*0602 alleles. No association was found between DPB1 alleles and antibodies reacting with U1A and SmD1 antigens. This first study reporting an association between autoantibodies reacting with U1A and SmD1 proteins (and peptides of these proteins), and immunogenetic markers suggest that the production of antibody subsets directed against different components (or regions of these proteins) bound to the same snRNP particle is associated with distinct MHC class II alleles.},
keywords = {Alleles, Antibody Specificity, Autoantibodies, Autoantigens, Autoimmune Diseases, Blotting, Dumortier, Enzyme-Linked Immunosorbent Assay, Genes, HLA-DP Antigens, HLA-DP beta-Chains, HLA-DQ Antigens, HLA-DQ beta-Chains, HLA-DR Antigens, HLA-DRB1 Chains, Humans, I2CT, MHC Class II, Peptides, Rheumatic Diseases, Ribonucleoprotein, Ribonucleoproteins, RNA-Binding Proteins, Small Nuclear, snRNP Core Proteins, Team-Dumortier, U1 Small Nuclear, Western},
pubstate = {published},
tppubtype = {article}
}
1998
Dumortier H, Gunnewiek J Klein, Roussel J P, van Aarssen Y, Briand J P, van Venrooij W J, Muller S
Dans: Nucleic Acids Research, vol. 26, no. 23, p. 5486–5491, 1998, ISSN: 0305-1048.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence, Animals, Dumortier, HeLa Cells, Humans, I2CT, Molecular Sequence Data, Peptide Fragments, Protein Binding, Rabbits, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Solutions, Spliceosomes, Team-Dumortier, U1 Small Nuclear, Zinc, Zinc Fingers
@article{dumortier_at_1998,
title = {At least three linear regions but not the zinc-finger domain of U1C protein are exposed at the surface of the protein in solution and on the human spliceosomal U1 snRNP particle},
author = {H Dumortier and J Klein Gunnewiek and J P Roussel and Y van Aarssen and J P Briand and W J van Venrooij and S Muller},
doi = {10.1093/nar/26.23.5486},
issn = {0305-1048},
year = {1998},
date = {1998-12-01},
journal = {Nucleic Acids Research},
volume = {26},
number = {23},
pages = {5486--5491},
abstract = {No structural information on U1C protein either in its free state or bound to the spliceosomal U1 small nuclear ribonucleoprotein (snRNP) particle is currently available. Using rabbit antibodies raised against a complete set of 15 U1C overlapping synthetic peptides (16-30 residues long) in different immunochemical tests, linear regions exposed at the surface of free and U1 snRNP-bound U1C were identified. Epitopes within at least three regions spanning residues 31-62, 85-103 and 116-159 were recognized on free and plastic-immobilized recombinant human U1C expressed in Escherichia coli, on in vitro translated U1C protein and on U1C bound to the U1 snRNP particle present in HeLa S100 extract. Using a zinc affinity labeling method, we further showed that the N-terminal U1C peptide containing a zinc-finger motif (peptide 5-34) effectively binds65Zn2+. The N-terminal region of U1C, which is functional in U1 snRNP assembly, is apparently not located at the surface of the U1 snRNP particle.},
keywords = {Amino Acid Sequence, Animals, Dumortier, HeLa Cells, Humans, I2CT, Molecular Sequence Data, Peptide Fragments, Protein Binding, Rabbits, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Solutions, Spliceosomes, Team-Dumortier, U1 Small Nuclear, Zinc, Zinc Fingers},
pubstate = {published},
tppubtype = {article}
}
Hoet R M, Raats J M, de Wildt R, Dumortier H, Muller S, van den Hoogen F, van Venrooij W J
Dans: Molecular Immunology, vol. 35, no. 16, p. 1045–1055, 1998, ISSN: 0161-5890.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence, Antibodies, Autoantibodies, Cross Reactions, Dumortier, Epitope Mapping, Genes, HeLa Cells, Humans, I2CT, Immunoglobulin, Immunoglobulin Fragments, Immunoglobulin Variable Region, Immunohistochemistry, Lupus Erythematosus, Monoclonal, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Systemic, Team-Dumortier, U1 Small Nuclear
@article{hoet_human_1998,
title = {Human monoclonal autoantibody fragments from combinatorial antibody libraries directed to the U1snRNP associated U1C protein; epitope mapping, immunolocalization and V-gene usage},
author = {R M Hoet and J M Raats and R de Wildt and H Dumortier and S Muller and F van den Hoogen and W J van Venrooij},
doi = {10.1016/s0161-5890(98)00093-5},
issn = {0161-5890},
year = {1998},
date = {1998-11-01},
journal = {Molecular Immunology},
volume = {35},
number = {16},
pages = {1045--1055},
abstract = {To study the localization and function of the U1snRNP associated U1C protein, so far only human sera from systemic lupus erythematosus (SLE) overlap syndrome patients have been used. Here we report for the first time the isolation of human monoclonal anti-UIC autoantibody fragments from IgG derived combinatorial and semi-synthetic human antibody libraries. Two classes of human monoclonal anti-UIC (auto)antibodies were found: specific anti-U1C autoantibodies, recognizing U1C only, and cross-reactive antibodies which also react with U1A and Sm-B/B'proteins. The heavy chains (V(H)genes) of all five antibodies from the semi-synthetic libraries and two of the three U1C-specific patient derived autoantibody fragments are encoded by V(H)3 genes, in which V(H) 3-30 (DP-49) was overrepresented. The heavy chain of the two cross-reactive autoantibodies are derived from the 3-07 (DP-54) gene. Three epitope regions on the U1C protein are targeted by these antibodies. (1) Four U1C specific antibodies recognize an N-terminal region of U1C in which amino acids 30-63 are essential for recognition, (2) two antibodies recognize only the complete U1C protein, and (3) two cross-reactive and one U1C specific antibody recognize the C-terminal domain in which amino acids 98-126 are critical for recognition. The two cross-reactive antibodies (K 11 and K 15) recognize the proline-rich region of the U1C protein (amino acids 98 126) and cross-react with proline-rich regions in Sm-B/B' (amino acids 163-184) and U1A (amino acids 187-204). All 10 antibody fragments are able to immunoprecipitate the native U1snRNP particle. The two cross-reactive antibodies immunoprecipitate the other Sm containing snRNPs as well. Using confocal immunofluorescence microscopy we could show that the major part of the U1C protein is localized within the coiled body structure.},
keywords = {Amino Acid Sequence, Antibodies, Autoantibodies, Cross Reactions, Dumortier, Epitope Mapping, Genes, HeLa Cells, Humans, I2CT, Immunoglobulin, Immunoglobulin Fragments, Immunoglobulin Variable Region, Immunohistochemistry, Lupus Erythematosus, Monoclonal, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Systemic, Team-Dumortier, U1 Small Nuclear},
pubstate = {published},
tppubtype = {article}
}