PMID- 22641694
OWN - NLM
STAT- MEDLINE
DCOM- 20130426
LR  - 20211021
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 125
IP  - Pt 18
DP  - 2012 Sep 15
TI  - Formation of telomeric repeat-containing RNA (TERRA) foci in highly proliferating 
      mouse cerebellar neuronal progenitors and medulloblastoma.
PG  - 4383-94
LID - 10.1242/jcs.108118 [doi]
AB  - Telomeres play crucial roles in the maintenance of genome integrity and control 
      of cellular senescence. Most eukaryotic telomeres can be transcribed to generate 
      a telomeric repeat-containing RNA (TERRA) that persists as a heterogeneous 
      nuclear RNA and can be developmentally regulated. However, the precise function 
      and regulation of TERRA in normal and cancer cell development remains poorly 
      understood. Here, we show that TERRA accumulates in highly proliferating normal 
      and cancer cells, and forms large nuclear foci, which are distinct from 
      previously characterized markers of DNA damage or replication stress. Using a 
      mouse model for medulloblastoma driven by chronic Sonic hedgehog (SHH) signaling, 
      TERRA RNA was detected in tumor, but not adjacent normal cells using both RNA 
      fluorescence in situ hybridization (FISH) and northern blotting. RNA FISH 
      revealed the formation of TERRA foci (TERFs) in the nuclear regions of rapidly 
      proliferating tumor cells. In the normal developing cerebellum, TERRA aggregates 
      could also be detected in highly proliferating zones of progenitor neurons. SHH 
      could enhance TERRA expression in purified granule progenitor cells in vitro, 
      suggesting that proliferation signals contribute to TERRA expression in 
      responsive tissue. TERRA foci did not colocalize with gammaH2AX foci, promyelocytic 
      leukemia (PML) or Cajal bodies in mouse tumor tissue. We also provide evidence 
      that TERRA is elevated in a variety of human cancers. These findings suggest that 
      elevated TERRA levels reflect a novel early form of telomere regulation during 
      replication stress and cancer cell evolution, and the TERRA RNA aggregates may 
      form a novel nuclear body in highly proliferating mammalian cells.
FAU - Deng, Zhong
AU  - Deng Z
AD  - Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, PA 
      19104, USA.
FAU - Wang, Zhuo
AU  - Wang Z
FAU - Xiang, Chaomei
AU  - Xiang C
FAU - Molczan, Aliah
AU  - Molczan A
FAU - Baubet, Valerie
AU  - Baubet V
FAU - Conejo-Garcia, Jose
AU  - Conejo-Garcia J
FAU - Xu, Xiaowei
AU  - Xu X
FAU - Lieberman, Paul M
AU  - Lieberman PM
FAU - Dahmane, Nadia
AU  - Dahmane N
LA  - eng
GR  - P30 CA010815/CA/NCI NIH HHS/United States
GR  - R01CA140652/CA/NCI NIH HHS/United States
GR  - P30 CA10815/CA/NCI NIH HHS/United States
GR  - R01 CA140652/CA/NCI NIH HHS/United States
GR  - R01 CA178687/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120528
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Histones)
RN  - 0 (Shh protein, mouse)
RN  - 0 (gamma-H2AX protein, mouse)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Animals
MH  - Brain/embryology/pathology
MH  - Cell Proliferation
MH  - Cerebellar Neoplasms/genetics/*pathology
MH  - Coiled Bodies/metabolism
MH  - DNA Damage
MH  - Disease Models, Animal
MH  - Gene Expression Regulation, Neoplastic
MH  - Hedgehog Proteins/pharmacology
MH  - Histones/metabolism
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Interphase
MH  - Medulloblastoma/*genetics/*pathology
MH  - Mice
MH  - Models, Biological
MH  - Neural Stem Cells/*metabolism/pathology
MH  - RNA/*genetics
MH  - Repetitive Sequences, Nucleic Acid/*genetics
MH  - Telomere/*genetics
PMC - PMC3516443
EDAT- 2012/05/30 06:00
MHDA- 2013/04/27 06:00
PMCR- 2013/09/15
CRDT- 2012/05/30 06:00
PHST- 2012/05/30 06:00 [entrez]
PHST- 2012/05/30 06:00 [pubmed]
PHST- 2013/04/27 06:00 [medline]
PHST- 2013/09/15 00:00 [pmc-release]
AID - jcs.108118 [pii]
AID - 10.1242/jcs.108118 [doi]
PST - ppublish
SO  - J Cell Sci. 2012 Sep 15;125(Pt 18):4383-94. doi: 10.1242/jcs.108118. Epub 2012 
      May 28.