title: SECIS-binding protein 2 interacts with the SMN complex and the methylosome for selenoprotein mRNP assembly and translation.
abstract: Selenoprotein synthesis requires the co-translational recoding of a UGASec codon. This process involves an RNA structural element, called Selenocysteine Insertion Sequence (SECIS) and the SECIS binding protein 2 (SBP2). Several selenoprotein mRNAs undergo unusual cap hypermethylation by the trimethylguanosine synthase 1 (Tgs1), which is recruited by the ubiquitous Survival of MotoNeurons (SMN) protein. SMN, the protein involved in spinal muscular atrophy, is part of a chaperone complex that collaborates with the methylosome for RNP assembly. Here, we analyze the role of individual SMN and methylosome components in selenoprotein mRNP assembly and translation. We show that SBP2 interacts directly with four proteins of the SMN complex and the methylosome core proteins. Nevertheless, SBP2 is not a methylation substrate of the methylosome. We found that both SMN and methylosome complexes are required for efficient translation of the selenoprotein GPx1 in vivo. We establish that the steady-state level of several selenoprotein mRNAs, major regulators of oxidative stress damage in neurons, is specifically reduced in the spinal cord of SMN-deficient mice and that cap hypermethylation of GPx1 mRNA is affected. Altogether we identified a new function of the SMN complex and the methylosome in selenoprotein mRNP assembly and expression.
authors.affiliation: Université de Strasbourg, Centre National de la Recherche Scientifique, Architecture et Réactivité de l'ARN, Institut de Biologie Moléculaire et Cellulaire, F-67000 Strasbourg, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Gribling-Burrer
authors.affiliation: Université de Strasbourg, Centre National de la Recherche Scientifique, Architecture et Réactivité de l'ARN, Institut de Biologie Moléculaire et Cellulaire, F-67000 Strasbourg, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Leichter
authors.affiliation: Université de Strasbourg, Centre National de la Recherche Scientifique, Architecture et Réactivité de l'ARN, Institut de Biologie Moléculaire et Cellulaire, F-67000 Strasbourg, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Wurth
authors.affiliation: Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine, Centre National de la Recherche Scientifique, UMR 7365, Faculté de Médecine, 54506 Vandoeuvre-les-Nancy Cedex, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Huttin
authors.affiliation: Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine, Centre National de la Recherche Scientifique, UMR 7365, Faculté de Médecine, 54506 Vandoeuvre-les-Nancy Cedex, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Schlotter
authors.affiliation: Département de Biologie Structurale Intégrative, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, CNRS UMR7104, INSERM U964, 67404 Illkirch, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Troffer-Charlier
authors.affiliation: Département de Biologie Structurale Intégrative, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, CNRS UMR7104, INSERM U964, 67404 Illkirch, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Cura
authors.affiliation: Université Pierre et Marie Curie, UMRS 974, INSERM, FRE3617, Institut de Myologie, 75013 Paris, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Barkats
authors.affiliation: Département de Biologie Structurale Intégrative, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, CNRS UMR7104, INSERM U964, 67404 Illkirch, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Cavarelli
authors.affiliation: Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine, Centre National de la Recherche Scientifique, UMR 7365, Faculté de Médecine, 54506 Vandoeuvre-les-Nancy Cedex, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Massenet
authors.affiliation: Université de Strasbourg, Centre National de la Recherche Scientifique, Architecture et Réactivité de l'ARN, Institut de Biologie Moléculaire et Cellulaire, F-67000 Strasbourg, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Allmang
mesh_terms: D005979:Glutathione Peroxidase; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D008954:Models, Biological; D009134:Muscular Atrophy, Spinal / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D055532:SMN Complex Proteins / Q000378:metabolism*; D051140:Selenoproteins / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
chemical_list: D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C121530:SECISBP2 protein, human; D055532:SMN Complex Proteins; D051140:Selenoproteins; C026452:messenger ribonucleoprotein; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human