Overview

The research in our lab centers on mechanisms of transcriptional regulation of gene expression. We are studying the transcription elongation and termination and factors that assist RNA polymerase II in transcription.

We have exploited yeast strains that show a novel regulatory mechanism of gene control that has shed light on the recently discovered world of transcripts that are unstable across genomes of many organisms. An unusual regulatory pathway determines where transcription of IMD2 starts as a function of the cellular GTP concentration. When GTP is abundant, transcription starts with a guanine nucleotide but the transcript terminates yielding a short non-coding RNA that is degraded; no Imd2 is made. When GTP is scarce, and Imd2 protein is needed, this start site is not used as transcription starts downstream from the termination site that yields the non-coding RNA. (Two opinion pieces describing our work and this mechanism are: B. Dichtl, 2008, Molec. Cell 31, 617 & Corden, 2008, EMBO Rep. 9:1084.) This termination mechanism is a specialized termination reaction used for small, often non-coding RNAs that employs RNA binding proteins and a helicase.

Using genetic assays, we have identified a region of an essential yeast protein, Nab3, that stitches together a complex of proteins that bind RNA and regulates expression at IMD2. Interestingly, this low complexity domain (it is almost 30% glutamine), has the aabilty to form amyloid polymers, a property of prions and other proteins that self-assemble and can cause disease in humans such as Alzheimers Disease, Huntingons Disease, and Lou Gehrigs Disease (Amyotrophic Lateral Sclerosis). We have found that there are subcategories of low complexity domains that can perform this function when they replace the native domain of Nab3. Current work focuses on why RNA binding proteins require this assembly domain and how polymerization is involved in its function.

Academic Appointment

• Professor of Biochemistry, Emory University School of Medicine

Education

Research