title: Striatal long noncoding RNA Abhd11os is neuroprotective against an N-terminal fragment of mutant huntingtin in vivo.
abstract: A large number of gene products that are enriched in the striatum have ill-defined functions, although they may have key roles in age-dependent neurodegenerative diseases affecting the striatum, especially Huntington disease (HD). In the present study, we focused on Abhd11os, (called ABHD11-AS1 in human) which is a putative long noncoding RNA (lncRNA) whose expression is enriched in the mouse striatum. We confirm that despite the presence of 2 small open reading frames (ORFs) in its sequence, Abhd11os is not translated into a detectable peptide in living cells. We demonstrate that Abhd11os levels are markedly reduced in different mouse models of HD. We performed in vivo experiments in mice using lentiviral vectors encoding either Abhd11os or a small hairpin RNA targeting Abhd11os. Results show that Abhd11os overexpression produces neuroprotection against an N-terminal fragment of mutant huntingtin, whereas Abhd11os knockdown is protoxic. These novel results indicate that the loss lncRNA Abhd11os likely contribute to striatal vulnerability in HD. Our study emphasizes that lncRNA may play crucial roles in neurodegenerative diseases.
authors.affiliation: CEA, DSV, I²BM, Molecular Imaging Research Center (MIRCen), Fontenay-aux-Roses, France; UMR 9199, CEA, CNRS, Université Paris-Sud, Neurodegenerative Diseases Laboratory, Fontenay-aux-Roses, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Francelle
authors.affiliation: CEA, DSV, I²BM, Molecular Imaging Research Center (MIRCen), Fontenay-aux-Roses, France; UMR 9199, CEA, CNRS, Université Paris-Sud, Neurodegenerative Diseases Laboratory, Fontenay-aux-Roses, France.
authors.forename: Laurie
authors.initials: L
authors.lastname: Galvan
authors.affiliation: CEA, DSV, I²BM, Molecular Imaging Research Center (MIRCen), Fontenay-aux-Roses, France; UMR 9199, CEA, CNRS, Université Paris-Sud, Neurodegenerative Diseases Laboratory, Fontenay-aux-Roses, France.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Gaillard
authors.affiliation: CEA, DSV, I²BM, Molecular Imaging Research Center (MIRCen), Fontenay-aux-Roses, France; UMR 9199, CEA, CNRS, Université Paris-Sud, Neurodegenerative Diseases Laboratory, Fontenay-aux-Roses, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Petit
authors.affiliation: CEA, iBiTecS, Gif-sur-Yvette Cedex, France; CNRS, FRE 3377, Gif-sur-Yvette Cedex, France; Université Paris-Sud, FRE 3377, Gif-sur-Yvette Cedex, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Bernay
authors.affiliation: CEA, DSV, I²BM, Molecular Imaging Research Center (MIRCen), Fontenay-aux-Roses, France; UMR 9199, CEA, CNRS, Université Paris-Sud, Neurodegenerative Diseases Laboratory, Fontenay-aux-Roses, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Guillermier
authors.affiliation: CEA, DSV, I²BM, Molecular Imaging Research Center (MIRCen), Fontenay-aux-Roses, France; UMR 9199, CEA, CNRS, Université Paris-Sud, Neurodegenerative Diseases Laboratory, Fontenay-aux-Roses, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Bonvento
authors.affiliation: CEA, DSV, I²BM, Molecular Imaging Research Center (MIRCen), Fontenay-aux-Roses, France; UMR 9199, CEA, CNRS, Université Paris-Sud, Neurodegenerative Diseases Laboratory, Fontenay-aux-Roses, France.
authors.forename: Noëlle
authors.initials: N
authors.lastname: Dufour
authors.affiliation: CEA, iBiTecS, Gif-sur-Yvette Cedex, France; CNRS, FRE 3377, Gif-sur-Yvette Cedex, France; Université Paris-Sud, FRE 3377, Gif-sur-Yvette Cedex, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Elalouf
authors.affiliation: CEA, DSV, I²BM, Molecular Imaging Research Center (MIRCen), Fontenay-aux-Roses, France; UMR 9199, CEA, CNRS, Université Paris-Sud, Neurodegenerative Diseases Laboratory, Fontenay-aux-Roses, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hantraye
authors.affiliation: CEA, DSV, I²BM, Molecular Imaging Research Center (MIRCen), Fontenay-aux-Roses, France; UMR 9199, CEA, CNRS, Université Paris-Sud, Neurodegenerative Diseases Laboratory, Fontenay-aux-Roses, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Déglon
authors.affiliation: CEA, iBiTecS, Gif-sur-Yvette Cedex, France; CNRS, FRE 3377, Gif-sur-Yvette Cedex, France; Université Paris-Sud, FRE 3377, Gif-sur-Yvette Cedex, France.
authors.forename: Michel
authors.initials: M
authors.lastname: de Chaldée
authors.affiliation: CEA, DSV, I²BM, Molecular Imaging Research Center (MIRCen), Fontenay-aux-Roses, France; UMR 9199, CEA, CNRS, Université Paris-Sud, Neurodegenerative Diseases Laboratory, Fontenay-aux-Roses, France. Electronic address: emmanuel.brouillet@cea.fr.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Brouillet
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D018696:Neuroprotective Agents; D009687:Nuclear Proteins / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D057057:Serine Proteases / Q000235:genetics* / Q000378:metabolism
chemical_list: C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; C568817:ABHD11 protein, human; D057057:Serine Proteases
keywords: Gene regulation; Huntington disease; Neurodegeneration; Neuroprotection; Noncoding RNA; Striatum