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


METHODS
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.


CONCLUSIONS
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.
Neplioueva
Valentina
V
Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America.
Dobrikova
Elena Y
EY
Mukherjee
Neelanjan
N
Keene
Jack D
JD
Gromeier
Matthias
M
D000818:Animals; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D008251:Macaca; D051379:Mice; D050779:Nuclear Factor 90 Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C429643:ILF3 protein, human; D050779:Nuclear Factor 90 Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger