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. 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

Infants’ early visual attention and social engagement as developmental precursors to joint attention.

This study examined infants’ early visual attention (at 1 month of age) and social engagement (4 months) as predictors of their later joint attention (12 and 18 months). The sample (n=325), drawn from the Maternal Lifestyle Study, a longitudinal multicenter project conducted at four centers of the NICHD Neonatal Research Network, included high-risk (cocaine exposed) and matched non-cocaine exposed infants. Hierarchical regressions revealed that infants’ attention orienting at 1 month significantly predicted more frequent initiating joint attention at 12 (but not 18) months of age. Social engagement at 4 months predicted initiating joint attention at 18 months. Results provide the first empirical evidence for the role of visual attention and social engagement behaviors as developmental precursors for later joint attention outcome