Joan Steitz, PhD

RNA-Protein Complexes: Roles in Gene Expression

Noncoding RNAs are important for every step of gene expression. We concentrate on nuclear noncoding RNAs complexed with proteins, where the most famous small nuclear RNPs (snRNPs) participate in pre-mRNA splicing. Current efforts are aimed at understanding how splicing influences downstream events in gene expression via the exon junction complex (EJC), how microRNA biogenesis is regulated during the nuclear maturation steps, and what is the mechanism and function of readthrough transcripts that arise from ~10% of human genes when cells are exposed to stress (osmotic, heat shock or oxidative). Some primate herpesviruses [Epstein-Barr virus (EBV), Herpesvirus saimiri (HVS), and Kaposi sarcoma virus (KSHV)] produce noncoding RNAs that associate with host cell proteins to form snRNPs. Recent investigations have uncovered an unexpected function for an abundant EBV snRNP in the production of viral particles – which is essential for oncogenesis. Other studies have revealed that the HSURs of HVS serve to upregulate genes that are hallmarks of T-cell activation in latently infected T cells — in part by binding and accelerating decay of a particular host microRNA. We have also characterized an RNA element in the PAN RNA of KSHV that counteracts a rapid nuclear RNA decay pathway and solved its high resolution structure, revealing its mechanism of action. Recently, we have discovered new modes of interaction of the polyA with upstream sequences in RNA molecules, most notably a 3'-end binding pocket, all composed completely of RNA.