Nuclear pre-messenger RNA transcripts in mammalian cells are complexed with proteins known as heterogeneous nuclear ribonucleoproteins (hnRNPs). hnRNP A1, a member of the hnRNP A/B family of proteins, shuttles between the nucleus and cytoplasm due to a nuclear transport signal in the gene termed M9. Based on its ability to shuttle and other data, it is argued by many that hnRNP A1 plays a central role in mRNA export. However, evidence thus far only implicates and does not directly prove this. Drosophila Melanogaster has two genes termed Hrb (for Heterogeneous nuclear RNA binding proteins) that encode functional homologues of the hnRNP A/B protein family. We will investigate the role of HRBs in mRNA export through the development of transgenic flies (by P element transformation) mutated in several domains of Hrb. A nonradioactive in situ hybridization assay will be developed to localize mRNA populations in wild type and mutant flies. This research will examine the posttranscriptiona control of normal gene expression in hopes of elucidating aberrant transcriptional processes that occur in diseases such as carcinogenesis.
