UC Berkeley

Nearly half of the human genome is composed of sequence encoding for elements known as retrotransposons. Although these non-coding RNA elements were initially considered to be “junk,” the last few decades have brought about a new appreciation for the importance of retrotransposons as dynamic players in a variety of host pathways. In Chapter I, I review the evolution of retrotransposons, and their architecture in mammalian genomes. I focus on the Short Interspersed Nuclear Elements (SINEs), a class of retrotransposon derived from host RNA polymerase III (RNAPIII)-transcribed genes. I describe their transcription by RNAPIII, as well as their functional relevance pre- and post-transcriptionally. I introduce B2 SINEs, a prominent murine SINE often used as a model to study SINE biology. These elements are highly induced during times of cellular stress, such as that caused by viral infection. Murine gammaherpesvirus 68 (MHV68) leads to a dramatic upregulation of B2 SINEs, which can influence viral gene transcription. In Chapter II, I present our investigation of the pathway to induction of B2 SINEs by MHV68 during infection, and our finding of the conserved herpesvirus kinase ORF36 as being able to induce these elements independently. In Chapter III, I discuss attempts to elucidate the functional relevance of B2 SINEs induced during infection. I describe an RNA-sequencing experiment done to examine changes in global transcription in the presence or absence of B2 SINEs during infection, as well as an experimental method to isolate B2 ncRNAs induced during infection, for potential use in downstream functional applications. In Chapter IV, I discuss perspectives on the presented data, and future directions for continued elucidation of the link between ORF36 and B2 SINE induction, as well as future directions for studying the functional relevance of induced elements. This study highlights the important role that retrotransposons, in particular SINE elements, play in host and viral pathways, and provides the first description of a herpesviral ORF that is able to induce these elements.