RNA Therapeutics Institute Publications

UMMS Affiliation

RNA Therapeutics Institute; Department of Neurology; Department of Medicine; Program in Molecular Medicine; Graduate School of Biomedical Sciences

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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


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.


ASOs, CAG repeat RNA foci, HTT mRNA, Huntington’s disease, RNA fluorescence in situ hybridization, confocal microscopy, siRNAs

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

DOI of Published Version



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

Journal/Book/Conference Title

Cell reports

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Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.