Tissue Type-Specific Expression of the dsRNA-Binding Protein 76 and Genome-wide Elucidation of its Target mRNAs

ABSTRACT: RNA-binding proteins accompany all steps in the life of mRNAs and provide dynamic gene regulation functions for rapid adjustment to changing extra- or intracellular conditions. The association of RNA-binding proteins with their targets is regulated through changing sub-cellular distribution, post-translational modification or association with other proteins. Tissue type-specific isoform distribution and target mRNA binding patterns are major determinants of post-transcriptional gene regulation by RNA-binding proteins.We demonstrate that the dsRNA binding protein 76 (DRBP76), synonymous with nuclear factor 90, displays inherently distinct tissue type-specific sub-cellular distribution in the normal human central nervous system and in malignant brain tumors of glial origin. Altered sub-cellular 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. Our data suggest that DRBP76 expression, isoform distribution and sub-cellular localization are profoundly disturbed upon malignant transformation in the CNS. Thus, DRBP76’s roles in co- or post-transcriptional gene regulation may contribute to the neoplastic phenotype. Keyword: RIP-chip 5 biological replicates of DRBP76 Immunoprecipitation samples, Mock Immunoprecipiation samples, Total mRNA samples were collected and analyzed using oligo microarrays. For each microarray, biological samples were labelled with Cy3 and human reference RNA was labelled with Cy5.

ORGANISM(S): Homo sapiens

SUBMITTER: Neplioueva V 

PROVIDER: S-ECPF-GEOD-20001 | biostudies-other | 2010

REPOSITORIES: biostudies-other