title: Hypermethylated-capped selenoprotein mRNAs in mammals.
abstract: Mammalian mRNAs are generated by complex and coordinated biogenesis pathways and acquire 5'-end m(7)G caps that play fundamental roles in processing and translation. Here we show that several selenoprotein mRNAs are not recognized efficiently by translation initiation factor eIF4E because they bear a hypermethylated cap. This cap modification is acquired via a 5'-end maturation pathway similar to that of the small nucle(ol)ar RNAs (sn- and snoRNAs). Our findings also establish that the trimethylguanosine synthase 1 (Tgs1) interacts with selenoprotein mRNAs for cap hypermethylation and that assembly chaperones and core proteins devoted to sn- and snoRNP maturation contribute to recruiting Tgs1 to selenoprotein mRNPs. We further demonstrate that the hypermethylated-capped selenoprotein mRNAs localize to the cytoplasm, are associated with polysomes and thus translated. Moreover, we found that the activity of Tgs1, but not of eIF4E, is required for the synthesis of the GPx1 selenoprotein in vivo.
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, 67084 Strasbourg, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Wurth
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, 67084 Strasbourg, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Gribling-Burrer
authors.affiliation: Equipe labélisée Ligue contre le cancer, Institut de Génétique Moléculaire, Centre National de la Recherche Scientifique, UMR 5535, 34293 Montpellier, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Verheggen
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, 67084 Strasbourg, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Leichter
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, 67084 Strasbourg, France.
authors.forename: Akiko
authors.initials: A
authors.lastname: Takeuchi
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, 67084 Strasbourg, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Baudrey
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, 67084 Strasbourg, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Martin
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, 67084 Strasbourg, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Krol
authors.affiliation: Equipe labélisée Ligue contre le cancer, Institut de Génétique Moléculaire, Centre National de la Recherche Scientifique, UMR 5535, 34293 Montpellier, France.
authors.forename: Edouard
authors.initials: E
authors.lastname: Bertrand
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, 67084 Strasbourg, France c.allmang@unistra.fr.
authors.forename: Christine
authors.initials: C
authors.lastname: Allmang
mesh_terms: D002460:Cell Line; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011132:Polyribosomes / Q000737:chemistry; D014176:Protein Biosynthesis; D012315:RNA Caps / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D020718:Ribonucleoproteins, Small Nucleolar / Q000378:metabolism; D055532:SMN Complex Proteins / Q000378:metabolism; D051140:Selenoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
chemical_list: D039561:Eukaryotic Initiation Factor-4E; C499062:NOP58 protein, human; D009687:Nuclear Proteins; D012315:RNA Caps; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D020718:Ribonucleoproteins, Small Nucleolar; C121530:SECISBP2 protein, human; D055532:SMN Complex Proteins; D051140:Selenoproteins; D005979:Glutathione Peroxidase; D008780:Methyltransferases; C456271:trimethylguanosine synthase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human