Beyer, Ann L.
- BS, Biochemistry, Centre College
- PhD, Molecular Biology, Vanderbilt University; Nashville TN
- Postdoc, Molecular Biology, University of Virginia
Ribosomal RNA transcription & processing
Current research in my laboratory is focused on understanding the basic cellular processes of ribosomal RNA (rRNA) transcription and ribosome biogenesis. We are interested in these questions because ribosome synthesis is strictly regulated and very tightly coupled to cell growth; it is up-regulated in cancer cells and thus is a target of some chemotherapies. We use an unusual electron microscopic approach called the Miller chromatin spreading method that allows us to directly visualize active rRNA genes. All of our studies are carried out in the yeast, Saccharomyces cerevisiae. In a typical approach, we first characterize parameters of interest in control cells and then compare them to the same parameters in cells with a genetic alteration of interest, such as depletion of a particular protein involved in the process being studied. This approach allows determination of the role of the protein in the process being studied. For study of transcriptional regulation, we analyze such parameters as the number of active rRNA genes in a nucleolus, transcription initiation and elongation rates for active genes, and chromatin structures correlated with various genetic activities. For the study of ribosome biogenesis, which begins while ribosomal RNA is being transcribed, we characterize structural details of early intermediates in small ribosomal subunit assembly that form on nascent transcripts. The type of data we obtain is very difficult to obtain using standard molecular biology approaches due to the multi-copy nature of rRNA genes and to the very short-lived nature of ribosome intermediates, but is very informative regarding molecular mechanism and structure. In recent studies (several cited below), we studied rRNA genes after significantly decreasing the number of rRNA genes per nucleolus, after interfering with the TOR signaling pathway, after depleting an RNA polymerase subunit, and after depletion of individual proteins essential for making ribosomes. Ongoing or planned studies are focusing on characterization of the composition of several short-lived intermediates in ribosome assembly, role of topoisomerases in rRNA transcription, role of chromatin structure and chromatin remodeling in rRNA transcription, and links between rRNA synthesis and nuclear export of ribosomal subunits.