Many mammalian and viral genes are alternatively spliced and subject to regulation at the post- transcriptional level. However, relatively little is known about the cellular mechanisms for this regulation. We are using retroviruses as model systems to elucidate these mechanisms. Some of our studies focus on HIV Rev, an essential HIV protein.Rev mediates the nucleo-cytoplasmic export of unspliced and incompletely spliced HIV RNAs and provides an important HIV drug target.
Another major focus of the laboratory is the function of the constitutive transport element (CTE). The CTE interacts directly with host cell proteins to facilitate export of intron containing RNA. We are currently analyzing the function of cellular proteins that are involved in the CTE mediated export pathway. One is NXF1 (TAP), a protein which has been proposed to play an essential role in cellular mRNA export. A second protein under study is NXT1, an important TAP cofactor. CTE function is also enhanced by SAM68, a major target of Src and Src family kinases and a potential tumor suppressor. Our studies are aimed at identifying the mechanism by which SAM68 promotes CTE function and the role that this protein plays in cellular gene regulation.