Research & Publications
Noncoding RNA-protein complexes (ncRNPs) are ubiquitous in eukaryotic cells and inhabit specific cellular compartments. The most famous noncoding nuclear RNPs (snRNPs) participate in pre-mRNA splicing by recognizing important intron signals and assembling to form an active splicing complex called the spliceosome. There are many other kinds, including those where the RNA is made by an infecting virus. Our recent contributions to understanding the roles of ncRNA-protein complexes in mammalian gene expression include: 1) The discovery that splicing-like snRNPs are made by a virus to degrade a host microRNA. 2) Finding that a viral noncoding RNA possesses an element that forms a triple helix with the polyA tail that serves to stabilize the RNA in the nucleus. 3) Finding that a viral noncoding RNA can direct a host transcription factor to the viral DNA.
Specialized Terms: Autoantibodies; Gene Expression; RNA; RNA Processing; SnRNPs; Viral Transformation
Extensive Research Description
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.
Autoantibodies; Biochemistry; Biophysics; Cell Transformation, Viral; RNA Processing, Post-Transcriptional; Gene Expression; Ribonucleoproteins, Small Nuclear