Nuclear Localization of Huntingtin mRNA Is Specific to Cells of Neuronal Origin
AuthorsDidiot, Marie C.
Ferguson, Chantal M.
Coles, Andrew H.
Smith, Abigail O.
Bicknell, Alicia A.
Hall, Lauren M.
Pai, Athma A.
Moore, Melissa J.
Hayward, Lawrence J.
UMass Chan AffiliationsGraduate School of Biomedical Sciences
Program in Molecular Medicine
Department of Medicine
Department of Neurology
RNA Therapeutics Institute
CAG repeat RNA foci
RNA fluorescence in situ hybridization
Cell and Developmental Biology
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Genetics and Genomics
Nervous System Diseases
Neuroscience and Neurobiology
Nucleic Acids, Nucleotides, and Nucleosides
MetadataShow full item record
AbstractHuntington's disease (HD) is a monogenic neurodegenerative disorder representing an ideal candidate for gene silencing with oligonucleotide therapeutics (i.e., antisense oligonucleotides [ASOs] and small interfering RNAs [siRNAs]). Using an ultra-sensitive branched fluorescence in situ hybridization (FISH) method, we show that approximately 50% of wild-type HTT mRNA localizes to the nucleus and that its nuclear localization is observed only in neuronal cells. In mouse brain sections, we detect Htt mRNA predominantly in neurons, with a wide range of Htt foci observed per cell. We further show that siRNAs and ASOs efficiently eliminate cytoplasmic HTT mRNA and HTT protein, but only ASOs induce a partial but significant reduction of nuclear HTT mRNA. We speculate that, like other mRNAs, HTT mRNA subcellular localization might play a role in important neuronal regulatory mechanisms.
Cell Rep. 2018 Sep 4;24(10):2553-2560.e5. doi: 10.1016/j.celrep.2018.07.106. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/48832
RightsThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Except where otherwise noted, this item's license is described as This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).