PMID- 27239700
OWN - NLM
STAT- MEDLINE
DCOM- 20190128
LR  - 20190128
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1862
IP  - 9
DP  - 2016 Sep
TI  - Nuclear speckles are detention centers for transcripts containing expanded CAG 
      repeats.
PG  - 1513-20
LID - S0925-4439(16)30132-6 [pii]
LID - 10.1016/j.bbadis.2016.05.015 [doi]
AB  - The human genetic disorders caused by CAG repeat expansions in the translated 
      sequences of various genes are called polyglutamine (polyQ) diseases because of 
      the cellular "toxicity" of the mutant proteins. The contribution of mutant 
      transcripts to the pathogenesis of these diseases is supported by several 
      observations obtained from cellular models of these disorders. Here, we show that 
      the common feature of cell lines modeling polyQ diseases is the formation of 
      nuclear CAG RNA foci. We performed qualitative and quantitative analyses of these 
      foci in numerous cellular models endogenously and exogenously expressing mutant 
      transcripts by fluorescence in situ hybridization (FISH). We compared the CAG RNA 
      foci of polyQ diseases with the CUG foci of myotonic dystrophy type 1 and found 
      substantial differences in their number and morphology. Smaller differences 
      within the polyQ disease group were also revealed and included a positive 
      correlation between the foci number and the CAG repeat length. We show that 
      expanded CAA repeats, also encoding glutamine, did not trigger RNA foci formation 
      and foci formation is independent of the presence of mutant polyglutamine 
      protein. Using FISH combined with immunofluorescence, we demonstrated partial 
      co-localization of CAG repeat foci with MBNL1 alternative splicing factor, which 
      explains the mild deregulation of MBNL1-dependent genes. We also showed that foci 
      reside within nuclear speckles in diverse cell types: fibroblasts, lymphoblasts, 
      iPS cells and neuronal progenitors and remain dependent on integrity of these 
      nuclear structures.
CI  - Copyright (c) 2016 Elsevier B.V. All rights reserved.
FAU - Urbanek, Martyna O
AU  - Urbanek MO
AD  - Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish 
      Academy of Sciences, Noskowskiego 12/14 Str., 61-704 Poznan, Poland.
FAU - Jazurek, Magdalena
AU  - Jazurek M
AD  - Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish 
      Academy of Sciences, Noskowskiego 12/14 Str., 61-704 Poznan, Poland.
FAU - Switonski, Pawel M
AU  - Switonski PM
AD  - Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish 
      Academy of Sciences, Noskowskiego 12/14 Str., 61-704 Poznan, Poland.
FAU - Figura, Grzegorz
AU  - Figura G
AD  - Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish 
      Academy of Sciences, Noskowskiego 12/14 Str., 61-704 Poznan, Poland.
FAU - Krzyzosiak, Wlodzimierz J
AU  - Krzyzosiak WJ
AD  - Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish 
      Academy of Sciences, Noskowskiego 12/14 Str., 61-704 Poznan, Poland. Electronic 
      address: wlodkrzy@ibch.poznan.pl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160527
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (HTT protein, human)
RN  - 0 (Huntingtin Protein)
RN  - 0 (MBNL1 protein, human)
RN  - 0 (Peptides)
RN  - 0 (RNA-Binding Proteins)
RN  - 26700-71-0 (polyglutamine)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Alternative Splicing
MH  - Animals
MH  - Cell Line
MH  - Cell Nucleus Structures/*genetics/*metabolism/pathology
MH  - HeLa Cells
MH  - Heredodegenerative Disorders, Nervous System/genetics/metabolism/pathology
MH  - Humans
MH  - Huntingtin Protein/genetics/metabolism
MH  - In Situ Hybridization, Fluorescence
MH  - Mice
MH  - Peptides/genetics/metabolism
MH  - RNA/genetics/metabolism
MH  - RNA-Binding Proteins/metabolism
MH  - Transcription, Genetic
MH  - *Trinucleotide Repeat Expansion
OTO - NOTNLM
OT  - CAG foci
OT  - CUG foci
OT  - Polyglutamine diseases
OT  - RNA toxicity
OT  - Splicing speckles
EDAT- 2016/05/31 06:00
MHDA- 2019/01/29 06:00
CRDT- 2016/05/31 06:00
PHST- 2016/04/06 00:00 [received]
PHST- 2016/05/18 00:00 [revised]
PHST- 2016/05/26 00:00 [accepted]
PHST- 2016/05/31 06:00 [entrez]
PHST- 2016/05/31 06:00 [pubmed]
PHST- 2019/01/29 06:00 [medline]
AID - S0925-4439(16)30132-6 [pii]
AID - 10.1016/j.bbadis.2016.05.015 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2016 Sep;1862(9):1513-20. doi: 
      10.1016/j.bbadis.2016.05.015. Epub 2016 May 27.