Our research focuses on the regulation of gene expression, in particular the mechanisms controlling cellular and viral mRNA expression. A critical step in the mRNA metabolism is the transport of the mRNA from the nucleus to the cytoplasm. Analysis of retroviral systems, pioneered by research on HIV-1, have shed light into some important aspects of nuclear mRNA export and have provided critical insights into mechanisms governing cellular mRNA and protein transport. We are utilizing retroviral systems to identify and study mechanisms of mRNA metabolism using a combination of biochemistry, functional genomics, and proteomics. The dissection of the mechanisms of posttranscriptional control and nucleocytoplasmic trafficking of macromolecules are relevant to understand processes involved in cellular gene expression as well as virus expression. Since posttranscriptional regulation is an essential step in virus propagation, our studies also focus on the understanding of this regulatory step in pathogenesis of HIV and SIV. We had previously identified NXF1 as the key nuclear receptor for cellular mRNAs, and we demonstrated that this function is conserved in metazoa. Recent data from my lab showed that some members of the NXF family participate in cytoplasmic mRNA trafficking. We have also identified and studied the mouse homologs of the human NXF1. We study a new type of RNA transport element, the RTE, which is present in LTR-retrotransposons. We performed a detailed structure-function analysis of RTE, which revealed that RTE, like the HIV-1 RRE, has a complex stem-loop structure essential for function. We identified the RNA binding motif 15 (RBM15) protein as the cellular factor that binds and exports RTE-containing mRNAs. RBM15 is a novel mRNA export factor and is linked to the NXF1 pathway. Thus, these experiments have identified another important factor of the mRNA export route.
