Nuclear Localization of Huntingtin mRNA Is Specific to Cells of Neuronal Origin
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Authors
Didiot, Marie C.Ferguson, Chantal M.
Ly, Socheata
Coles, Andrew H.
Smith, Abigail O
Bicknell, Alicia A.
Hall, Lauren M.
Sapp, Ellen
Echeverria, Dimas
Pai, Athma A
DiFiglia, Marian
Moore, Melissa J.
Hayward, Lawrence J.
Aronin, Neil
Khvorova, Anastasia
UMass Chan Affiliations
Graduate School of Biomedical SciencesProgram in Molecular Medicine
Department of Medicine
Department of Neurology
RNA Therapeutics Institute
Document Type
Journal ArticlePublication Date
2018-09-04Keywords
ASOsCAG repeat RNA foci
HTT mRNA
Huntington’s disease
RNA fluorescence in situ hybridization
confocal microscopy
siRNAs
Cell and Developmental Biology
Cells
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Genetic Phenomena
Genetics and Genomics
Nervous System Diseases
Neuroscience and Neurobiology
Nucleic Acids, Nucleotides, and Nucleosides
Metadata
Show full item recordAbstract
Huntington'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.Source
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
DOI
10.1016/j.celrep.2018.07.106Permanent Link to this Item
http://hdl.handle.net/20.500.14038/48832PubMed ID
30184490Related Resources
Rights
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2018.07.106
Scopus Count
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/).