President's Distinguished Lecture I

Joan A. Steitz, PhD 
Department of Molecular Biophysics and Biochemistry
Yale University School of Medicine 
New Haven, CT, USA

Friday, March 13
8:30 a.m. - 9:30 a.m.
President's Distinguished Lecture I: Viral Noncoding RNAs: Approaching Answers

Noncoding (nc)RNAs play pivotal roles in the regulation of gene expression, but exhibit a diversity of functions whether encoded by cellular or viral genomes. Our studies of ncRNAs produced by the oncogenic gamma herpesviruses illustrate the habit of viruses to acquire components from their host cells but then utilize them – sometimes in quite different ways – to enhance the viral life cycle.

Studies of a herpesviral ncRNA called HSUR1 from Herpesvirus saimiri (HVS) have provided insights into an important but poorly-understood cellular regulatory mechanism called target-directed miRNA decay (TDMD). In collaboration with Ian MacRae’s lab at Scripps Institute, we have obtained X-ray structures of human Ago2 bound simultaneously to miRNAs and TDMD-inducing targets. These explain how specific miRNA/target interactions can lead to miRNA decay, with implications for how cellular miRNA populations can be regulated.

Another example is the use of RNA elements called ENEs by both viruses and cells to stabilize transcripts by engaging the polyA tail or 3’-terminal A-rich tract in a triple-helical RNA structure that obstructs the initiation of degradation. Our structural studies of ENEs from the PAN ncRNA of the oncogenic virus KSHV, from the vertebrate long ncRNA MALAT1 and recently double ENEs complexed with PolyA have led to unanticipated insights into the structure of RNA triple helices and associated RNA interactions important for stabilizing RNAs inside cells.