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.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Francelle L,Galvan L,Gaillard MC,Petit F,Bernay B,Guillermier M,Bonvento G,Dufour N,Elalouf JM,Hantraye P,Déglon N,de Chaldée M,Brouillet E

doi

10.1016/j.neurobiolaging.2014.11.014

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

1601.e7-16

issue

3

eissn

0197-4580

issn

1558-1497

pii

S0197-4580(14)00785-4

journal_volume

36

pub_type

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