Tissue type-specific expression of the dsRNA-binding protein 76 and genome-wide elucidation of its target mRNAs.
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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.
Cell Line, Tumor
Fluorescent Antibody Technique
In Vitro Techniques
Nuclear Factor 90 Proteins
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
Published Version (Please cite this version)10.1371/journal.pone.0011710
Publication InfoNeplioueva, 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.
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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
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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