number of access : ?
number of downloads : ?
ID 112030
Title Alternative
ヌクレオリンは、超保存領域を含むTRA2β4を核内に保持し、大腸がん細胞の増殖を促進する
Author
Satake, Yuzuru Tokushima University
Nishikawa, Tatsuya Tokushima University
Fujita, Kinuyo Tokushima University
Saijo, Saki Tokushima University
Itai, Miki Tokushima University
Tanaka, Hiroki Tokushima University
Keywords
nucleolin
transcribed-UCR
TRA2β4
colon cancer
cell growth
Content Type
Thesis or Dissertation
Description
Transcribed-ultraconserved regions (T-UCRs), which contain conserved sequences with 100% identity across human, rat and mouse species, are a novel category of functional RNAs. The human transformer 2β gene (TRA2B) encodes a UCR that spans exon 2 (276 bp) and its neighboring introns. Among five spliced RNA variants (TRA2β1-5) transcribed from the TRA2B gene, only TRA2β4 contains the conserved exon 2. TRA2β4 is overexpressed in colon cancer cells and accelerates cell growth by blocking the transcription of CDKN1A. However, the mechanisms underlying the overexpression of TRA2β4 in colon cancer cells are unknown. Using biotinylated RNA pull-down assays followed by liquid chromatography-mass spectrometric analysis, we identified nucleolin as a TRA2β4-binding protein. Knockdown of nucleolin reduced the nuclear retention of TRA2β4 and accelerated its degradation in the cytoplasm, whereas nucleolin overexpression increased TRA2β4 levels and its mitogenic activity. Nucleolin directly bound to TRA2β4 exon 2 via the glycine/arginine-rich (GAR) domain. Overexpression of GAR-deficient nucleolin failed to increase TRA2β4 expression and growth of colon cancer cells. RNA fluorescence in situ hybridization showed that TRA2β4 co-localized with nucleolin in nuclei but not with the mutant lacking GAR. Our results suggest that specific interactions between nucleolin and UCR-containing TRA2β4 may be associated with abnormal growth of colon cancer cells.
Journal Title
Oncotarget
ISSN
19492553
Publisher
Impact Journals
Volume
9
Issue
42
Start Page
26817
End Page
26833
Published Date
2018-06-01
Remark
内容要旨・審査要旨・論文本文の公開
本論文は, 著者Yuzuru Satakeの学位論文として提出され, 学位審査・授与の対象となっている。
Rights
Copyright: Satake et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ( https://creativecommons.org/licenses/by/3.0/ )
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3201号
Diploma Number
甲医第1376号
Granted Date
2018-07-26
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences