Our Faculty > Ann L. Beyer

Ann L. Beyer

Ann L. Beyer

Education

  • BS, Centre College of Kentucky; Danville KY
  • PhD, Vanderbilt University; Nashville TN
  • Postdoc, University of Virgina

Primary Appointment

  • Professor, Microbiology, Immunology, and Cancer Biology

Contact

Research Interest(s)

Ribosomal RNA transcription & processing

Research Description

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.


Selected Publications

  • Schneider D, French S, Osheim Y, Bailey A, Vu L, Dodd J, Yates J, Beyer A, Nomura M. RNA polymerase II elongation factors Spt4p and Spt5p play roles in transcription elongation by RNA polymerase I and rRNA processing. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(34): 12707-12. PMID: 16908835 | PMCID: PMC1568913
  • Bleichert F, Granneman S, Osheim Y, Beyer A, Baserga S. The PINc domain protein Utp24, a putative nuclease, is required for the early cleavage steps in 18S rRNA maturation. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(25): 9464-9. PMID: 16769905 | PMCID: PMC1480430
  • Dasgupta A, Sprouse R, French S, Aprikian P, Hontz R, Juedes S, Smith J, Beyer A, Auble D. Regulation of rRNA synthesis by TATA-binding protein-associated factor Mot1. Molecular and cellular biology. 2007;27(8): 2886-96. PMID: 17296733 | PMCID: PMC1899949
  • Schneider D, Michel A, Sikes M, Vu L, Dodd J, Salgia S, Osheim Y, Beyer A, Nomura M. Transcription elongation by RNA polymerase I is linked to efficient rRNA processing and ribosome assembly. Molecular cell. 2007;26(2): 217-29. PMID: 17466624 | PMCID: PMC1927085
  • Hontz R, French S, Oakes M, Tongaonkar P, Nomura M, Beyer A, Smith J. Transcription of multiple yeast ribosomal DNA genes requires targeting of UAF to the promoter by Uaf30. Molecular and cellular biology. 2008;28(21): 6709-19. PMID: 18765638 | PMCID: PMC2573240
  • Vanrobays E, Leplus A, Osheim Y, Beyer A, Wacheul L, Lafontaine D. TOR regulates the subcellular distribution of DIM2, a KH domain protein required for cotranscriptional ribosome assembly and pre-40S ribosome export. RNA (New York, N.Y.). 2008;14(10): 2061-73. PMID: 18755838 | PMCID: PMC2553727
  • Segerstolpe A, Lundkvist P, Osheim Y, Beyer A, Wieslander L. Mrd1p binds to pre-rRNA early during transcription independent of U3 snoRNA and is required for compaction of the pre-rRNA into small subunit processomes. Nucleic acids research. 2008;36(13): 4364-80. PMID: 18586827 | PMCID: PMC2490760
  • French S, Osheim Y, Schneider D, Sikes M, Fernandez C, Copela L, Misra V, Nomura M, Wolin S, Beyer A. Visual analysis of the yeast 5S rRNA gene transcriptome: regulation and role of La protein. Molecular and cellular biology. 2008;28(14): 4576-87. PMID: 18474615 | PMCID: PMC2447126
  • Osheim Y, French S, Sikes M, Beyer A. Electron microscope visualization of RNA transcription and processing in Saccharomyces cerevisiae by Miller chromatin spreading. Methods in molecular biology (Clifton, N.J.). 2008;464 55-69. PMID: 18951179
  • Lundkvist P, Jupiter S, Segerstolpe A, Osheim Y, Beyer A, Wieslander L. Mrd1p is required for release of base-paired U3 snoRNA within the preribosomal complex. Molecular and cellular biology. 2009;29(21): 5763-74. PMID: 19704003 | PMCID: PMC2772733
  • Zhang Y, Sikes M, Beyer A, Schneider D. The Paf1 complex is required for efficient transcription elongation by RNA polymerase I. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(7): 2153-8. PMID: 19164765 | PMCID: PMC2650124
  • French S, Sikes M, Hontz R, Osheim Y, Lambert T, El Hage A, Smith M, Tollervey D, Smith J, Beyer A. Distinguishing the roles of Topoisomerases I and II in relief of transcription-induced torsional stress in yeast rRNA genes. Molecular and cellular biology. 2010;31(3): 482-94. PMID: 21098118 | PMCID: PMC3028620
  • El Hage A, French S, Beyer A, Tollervey D. Loss of Topoisomerase I leads to R-loop-mediated transcriptional blocks during ribosomal RNA synthesis. Genes & development. 2010;24(14): 1546-58. PMID: 20634320 | PMCID: PMC2904944