RNA-Protein Complexes: Roles in Gene Expression

RNA-protein complexes (RNPs) are important for every step of gene expression. We concentrate on RNPs of the nucleus, 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 splicing is linked to 3'-end formation and export, and how guide RNAs modify the snRNA components of snRNPs. Recently, we have found that 3'-end formation of histone mRNAs, which lack polyA tails, employs many of the same factors that are needed for the cleavage and polyadenylation of most mRNAs.

Some primate herpesviruses [Epstein-Barr virus (EBV), Herpesvirus saimiri (HVS), and Kaposi sarcoma virus (KSHV)] encode small RNAs that associate with host cell proteins to form snRNPs. Recent investigations have studied the protein binding and nuclear localization of the EBERs of EBV, have revealed that the HSURs of HVS serve to upregulate genes that are hallmarks of T-cell activation in latently infected T cells, and have uncovered an RNA element in the PAN RNA of KSHV that counteracts a rapid nuclear RNA decay pathway and therefore provides a handle for studying a new form of nuclear mRNA surveillance.

We have discovered a novel polyA-binding protein specific for early development called ePAB in both Xenopus and mouse cells. We are investigating the roles of both proteins and microRNAs that bind to the 3' UTR to control mRNA translation, including the surprising finding that proteins considered repressive (such as FXR1 and AGO2) can upregulate translation under certain physiological conditions. Finally, we are studying the biogenesis of microRNAs, which are fashioned from longer precursors within the cell nucleus before trimming and assembly into microRNPs that control translation in the cytoplasm.