PMID- 30184490
OWN - NLM
STAT- MEDLINE
DCOM- 20191125
LR  - 20201113
IS  - 2211-1247 (Electronic)
VI  - 24
IP  - 10
DP  - 2018 Sep 4
TI  - Nuclear Localization of Huntingtin mRNA Is Specific to Cells of Neuronal Origin.
PG  - 2553-2560.e5
LID - S2211-1247(18)31239-7 [pii]
LID - 10.1016/j.celrep.2018.07.106 [doi]
AB  - 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.
CI  - Published by Elsevier Inc.
FAU - Didiot, Marie-Cecile
AU  - Didiot MC
AD  - RNA Therapeutics Institute, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA. Electronic address: marie.didiot@umassmed.edu.
FAU - Ferguson, Chantal M
AU  - Ferguson CM
AD  - RNA Therapeutics Institute, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - Ly, Socheata
AU  - Ly S
AD  - RNA Therapeutics Institute, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - Coles, Andrew H
AU  - Coles AH
AD  - RNA Therapeutics Institute, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - Smith, Abigail O
AU  - Smith AO
AD  - RNA Therapeutics Institute, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - Bicknell, Alicia A
AU  - Bicknell AA
AD  - RNA Therapeutics Institute, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - Hall, Lauren M
AU  - Hall LM
AD  - RNA Therapeutics Institute, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - Sapp, Ellen
AU  - Sapp E
AD  - MassGeneral Institute for Neurodegenerative Disease, Massachusetts General 
      Hospital, Charlestown, MA 02129, USA.
FAU - Echeverria, Dimas
AU  - Echeverria D
AD  - RNA Therapeutics Institute, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - Pai, Athma A
AU  - Pai AA
AD  - RNA Therapeutics Institute, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - DiFiglia, Marian
AU  - DiFiglia M
AD  - MassGeneral Institute for Neurodegenerative Disease, Massachusetts General 
      Hospital, Charlestown, MA 02129, USA.
FAU - Moore, Melissa J
AU  - Moore MJ
AD  - RNA Therapeutics Institute, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - Hayward, Lawrence J
AU  - Hayward LJ
AD  - Department of Neurology, University of Massachusetts Medical School, Worcester, 
      MA 01605, USA.
FAU - Aronin, Neil
AU  - Aronin N
AD  - RNA Therapeutics Institute, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA; Department of Medicine, University of Massachusetts 
      Medical School, Worcester, MA 01605, USA.
FAU - Khvorova, Anastasia
AU  - Khvorova A
AD  - RNA Therapeutics Institute, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA; Program in Molecular Medicine, University of 
      Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: 
      anastasia.khvorova@umassmed.edu.
LA  - eng
GR  - R01 NS104022/NS/NINDS NIH HHS/United States
GR  - S10 OD020012/OD/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Animals
MH  - Cell Nucleus/metabolism
MH  - Cells, Cultured
MH  - Female
MH  - Gene Silencing
MH  - HeLa Cells
MH  - Humans
MH  - Huntington Disease/*metabolism
MH  - In Situ Hybridization, Fluorescence
MH  - Mice
MH  - Neurons/*cytology/*metabolism
MH  - Oligonucleotides, Antisense/genetics
MH  - RNA, Messenger/genetics/*metabolism
MH  - RNA, Small Interfering/genetics/physiology
MH  - Trinucleotide Repeat Expansion/genetics
PMC - PMC6245656
MID - NIHMS1506727
OTO - NOTNLM
OT  - ASOs
OT  - CAG repeat RNA foci
OT  - HTT mRNA
OT  - Huntington's disease
OT  - RNA fluorescence in situ hybridization
OT  - confocal microscopy
OT  - siRNAs
EDAT- 2018/09/06 06:00
MHDA- 2019/11/26 06:00
PMCR- 2018/11/20
CRDT- 2018/09/06 06:00
PHST- 2017/12/20 00:00 [received]
PHST- 2018/06/30 00:00 [revised]
PHST- 2018/07/30 00:00 [accepted]
PHST- 2018/09/06 06:00 [entrez]
PHST- 2018/09/06 06:00 [pubmed]
PHST- 2019/11/26 06:00 [medline]
PHST- 2018/11/20 00:00 [pmc-release]
AID - S2211-1247(18)31239-7 [pii]
AID - 10.1016/j.celrep.2018.07.106 [doi]
PST - ppublish
SO  - Cell Rep. 2018 Sep 4;24(10):2553-2560.e5. doi: 10.1016/j.celrep.2018.07.106.