caa a22 4500 397575688 CHVBK 20180308164855.0 cr unu---uuuuu 161202e199601 xx s 000 0 eng 10.1093/hmg/5.1.95 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.1.95 Alternative Splicing of Exon 14 Determines Nuclear or Cytoplasmic Localisation of FMR1 Protein Isoforms [Elektronische Daten] [Annie Sittler, Didier Devys, Chantal Weber, Jean-Louis Mandel] Impaired expression of the FMR1 gene is responsible for the fragile X mental retardation syndrome. The FMR1 gene encodes a cytoplasmic protein with RNA-binding properties. Its complex alternative splicing leads to several isoforms, whose abundance and specific functions in the cell are not known. We have cloned in expression vectors, cDNAs corresponding to several isoforms. Western blot comparison of the pattern of endogenous FMR1 proteins with these transfected isoforms allowed the tentative identification of the major endogenous isoform as ISO 7 and of a minor band as an isoform lacking exon 14 sequences (ISO 6 or ISO 12), while some other isoforms (ISO 4, ISO 5) were not expressed at detectable levels. Surprisingly, in immunofluorescence studies, the transfected splice variants that exclude exon 14 sequences (and have alternate C-terminal regions) were shown to be nuclear. Such differential localisation was however not seen in subcellular fractionation studies. Analysis of various deletion mutants suggests the presence of a cytoplasmic retention domain encoded in exon 14 and of a nuclear association domain encoded within the first eight exons that appear however to lack a typical nuclear localisation signal. © 1996 Oxford University Press Sittler Annie Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, ULP, 1 rue Laurent Fries, BP 163, 67404 Illkirch Cédex, C.U. de Strasbourg, France aut Devys Didier Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, ULP, 1 rue Laurent Fries, BP 163, 67404 Illkirch Cédex, C.U. de Strasbourg, France aut Weber Chantal Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, ULP, 1 rue Laurent Fries, BP 163, 67404 Illkirch Cédex, C.U. de Strasbourg, France aut Mandel Jean-Louis Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, ULP, 1 rue Laurent Fries, BP 163, 67404 Illkirch Cédex, C.U. de Strasbourg, France aut Human Molecular Genetics Oxford University Press 5/1(1996-01), 95-102 0964-6906 5:1<95 1996 5 hmg https://doi.org/10.1093/hmg/5.1.95 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.1.95 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sittler Annie Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, ULP, 1 rue Laurent Fries, BP 163, 67404 Illkirch Cédex, C.U. de Strasbourg, France aut NATIONALLICENCE 700 1- Devys Didier Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, ULP, 1 rue Laurent Fries, BP 163, 67404 Illkirch Cédex, C.U. de Strasbourg, France aut NATIONALLICENCE 700 1- Weber Chantal Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, ULP, 1 rue Laurent Fries, BP 163, 67404 Illkirch Cédex, C.U. de Strasbourg, France aut NATIONALLICENCE 700 1- Mandel Jean-Louis Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, ULP, 1 rue Laurent Fries, BP 163, 67404 Illkirch Cédex, C.U. de Strasbourg, France aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/1(1996-01), 95-102 0964-6906 5:1<95 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford