Tissue type-specific expression of the dsRNA-binding protein 76 and genome-wide elucidation of its target mRNAs.

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Neplioueva, Valentina

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Dobrikova, Elena Y

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Mukherjee, Neelanjan

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Keene, Jack D

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Gromeier, Matthias

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United States

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2011-06-21T17:31:33Z

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2010-07-23

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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.

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Version of Record

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https://www.ncbi.nlm.nih.gov/pubmed/20668518

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1932-6203

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https://hdl.handle.net/10161/4556

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eng

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en_US

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Public Library of Science (PLoS)

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PLoS One

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10.1371/journal.pone.0011710

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Plos One

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Animals

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Brain

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Cell Line

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Cell Line, Tumor

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Fluorescent Antibody Technique

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Humans

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Immunoblotting

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In Vitro Techniques

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Macaca

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Mice

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Nuclear Factor 90 Proteins

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Oligonucleotide Array Sequence Analysis

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Protein Isoforms

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RNA, Messenger

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Reverse Transcriptase Polymerase Chain Reaction

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Tissue type-specific expression of the dsRNA-binding protein 76 and genome-wide elucidation of its target mRNAs.

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dc.type

Journal article

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2010-7-23

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7

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5

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https://www.ncbi.nlm.nih.gov/pubmed/20668518

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e11710

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7

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Basic Science Departments

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Clinical Science Departments

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Duke

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Duke Cancer Institute

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Institutes and Centers

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Medicine

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Medicine, Infectious Diseases

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Medicine, Rheumatology and Immunology

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Molecular Genetics and Microbiology

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Neurosurgery

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School of Medicine

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Published online

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5

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