Abstract：
: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 ∼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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Didiot MC,Ferguson CM,Ly S,Coles AH,Smith AO,Bicknell AA,Hall LM,Sapp E,Echeverria D,Pai AA,DiFiglia M,Moore MJ,Hayward LJ,Aronin N,Khvorova Adoi
10.1016/j.celrep.2018.07.106subject
Has Abstractpub_date
2018-09-04 00:00:00pages
2553-2560.e5issue
10issn
2211-1247pii
S2211-1247(18)31239-7journal_volume
24pub_type
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