Tissue type-specific expression of the dsRNA-binding protein 76 and genome-wide elucidation of its target mRNAs.
Abstract
BACKGROUND: RNA-binding proteins accompany all steps in the life of mRNAs and provide
dynamic gene regulatory functions for rapid adjustment to changing extra- or intracellular
conditions. The association of RNA-binding proteins with their targets is regulated
through changing subcellular distribution, post-translational modification or association
with other proteins. METHODOLOGY: We demonstrate that the dsRNA binding protein 76
(DRBP76), synonymous with nuclear factor 90, displays inherently distinct tissue type-specific
subcellular distribution in the normal human central nervous system and in malignant
brain tumors of glial origin. Altered subcellular localization and isoform distribution
in malignant glioma indicate that tumor-specific changes in DRBP76-related gene products
and their regulatory functions may contribute to the formation and/or maintenance
of these tumors. To identify endogenous mRNA targets of DRBP76, we performed RNA-immunoprecipitation
and genome-wide microarray analyses in HEK293 cells, and identified specific classes
of transcripts encoding critical functions in cellular metabolism. SIGNIFICANCE: Our
data suggest that physiologic DRBP76 expression, isoform distribution and subcellular
localization are profoundly altered upon malignant transformation. Thus, the functional
role of DRBP76 in co- or post-transcriptional gene regulation may contribute to the
neoplastic phenotype.
Type
Journal articleSubject
AnimalsBrain
Cell Line
Cell Line, Tumor
Fluorescent Antibody Technique
Humans
Immunoblotting
In Vitro Techniques
Macaca
Mice
Nuclear Factor 90 Proteins
Oligonucleotide Array Sequence Analysis
Protein Isoforms
RNA, Messenger
Reverse Transcriptase Polymerase Chain Reaction
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https://hdl.handle.net/10161/4556Published Version (Please cite this version)
10.1371/journal.pone.0011710Publication Info
Neplioueva, Valentina; Dobrikova, Elena Y; Mukherjee, Neelanjan; Keene, Jack D; &
Gromeier, Matthias (2010). Tissue type-specific expression of the dsRNA-binding protein 76 and genome-wide elucidation
of its target mRNAs. PLoS One, 5(7). pp. e11710. 10.1371/journal.pone.0011710. Retrieved from https://hdl.handle.net/10161/4556.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Matthias Gromeier
Professor of Neurosurgery
I am a classically trained virologist with a focus on molecular mechanisms of RNA
virus pathogenesis. My career is dedicated to unraveling RNA virus:host relations
and devising methods of exploiting them for cancer immunotherapy and vaccine design.
My background is in translation regulation and mRNA metabolism, viral RNA sensing
and innate immunity, and cancer immunology and immunotherapy. Basic mechanistic research
in my laboratory is supporting an ambitious clinical translational research prog
Jack Donald Keene
James B. Duke Distinguished Professor of Molecular Genetics and Microbiology
The Keene Laboratory has a long-term interest in the structure and function of viral
and mammalian genomes. Having determined the first genomic sequences for rabies, Ebola,
Marburg and vesicular stomatitis virus, and discerned the origins of defective interfering
viruses, interests shifted to the cloning of six human genes involved in autoimmune
reactivity. This resulted in the identification of numerous autoimmune RRM-type RNA-binding
proteins the discovery of the RRM, and the RNA targets
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