Nucleolin facilitates nuclear retention of an ultraconserved region containing TRA2β4 and accelerates colon cancer cell growth
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 gene ( ) encodes a UCR that spans exon 2 (276 bp) and its neighboring introns. Among five spliced RNA variants ( )...
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Published in | Oncotarget Vol. 9; no. 42; pp. 26817 - 26833 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Impact Journals LLC
01.06.2018
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Subjects | |
Online Access | Get full text |
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Summary: | 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
gene (
) encodes a UCR that spans exon 2 (276 bp) and its neighboring introns. Among five spliced RNA variants (
) transcribed from the
gene, only
contains the conserved exon 2.
is overexpressed in colon cancer cells and accelerates cell growth by blocking the transcription of
. However, the mechanisms underlying the overexpression of
in colon cancer cells are unknown. Using biotinylated RNA pull-down assays followed by liquid chromatography-mass spectrometric analysis, we identified nucleolin as a
-binding protein. Knockdown of nucleolin reduced the nuclear retention of
and accelerated its degradation in the cytoplasm, whereas nucleolin overexpression increased
levels and its mitogenic activity. Nucleolin directly bound to
exon 2 via the glycine/arginine-rich (GAR) domain. Overexpression of GAR-deficient nucleolin failed to increase
expression and growth of colon cancer cells. RNA fluorescence
hybridization showed that
co-localized with nucleolin in nuclei but not with the mutant lacking GAR. Our results suggest that specific interactions between nucleolin and UCR-containing
may be associated with abnormal growth of colon cancer cells. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1949-2553 1949-2553 |
DOI: | 10.18632/oncotarget.25510 |