Masayasu Nomura
Grace Bell Professor, Biological Chemistry
School of Medicine
School of Medicine
Microbiology & Molecular Genetics
School of Medicine
School of Medicine
PH.D., University of Tokyo, 1957
University of California, Irvine
109 Plumwood House
Mail Code: 1700
Irvine, CA 92697
109 Plumwood House
Mail Code: 1700
Irvine, CA 92697
Research Interests
RNA Polymerase I; ribosome synthesis; growth regulation.
Research Abstract
The Nomura laboratory studies the regulation of ribosome synthesis, specifically the transcription of rDNA by RNA polymerase I (Pol I) in the yeast Saccharomyces cerevisiae. Their approach has been to isolate many mutants (rrn mutants) that are defective in rDNA transcription by Pol I. By analyzing these mutants, twelve genes have been identified and characterized that are uniquely involved in Pol I transcription. Five of these genes encode specific Pol I subunits. The remaining genes encode subunits of Pol I specific transcription factors. By carrying out genetic and in vitro rDNA transcription experiments, they have identified and purified three transcription factors and defined their roles in the initiation of transcription. One of these factors, UAF, which is required for a high level of rDNA transcription, was found to contain histones H3 and H4 and may be considered as part of rDNA specific chromatins. Current work in the laboratory includes in vitro and in vivo experiments to clarify roles of individual subunits of these factors, including their role in rDNA specific chromatin structures, and to understand detailed mechanisms of Pol I-directed rDNA transcription and its regulation.
Workers in the Nomura laboratory are also studying nuclear and nucleolar structures in connection with Pol I function and ribosome biosynthesis. Transcription of rDNA occurs in the nucleolus. Recent experiments have shown that the presence of Pol I and Pol I-specific transcription factors are important for the maintenance of proper nucleolar structures. Genetic and biochemical approaches combined with cytological analyses are being used in this study. For example, they have discovered that yeast mutants defective in transcription factor UAF give rise to variants able to grow by transcribing endogenous rDNA by RNA polymerase II (Pol II). They have also discovered that the switch to growth using the Pol II system consists of two steps: a mutational alteration in UAF and an expansion of chromosomal rDNA repeats. This phenomenon is being studied in connection with the plasticity of nucleolar structures and its biological significance.
In connection with the above studies, it was shown that silencing of Pol II reporter genes integrated in rDNA repeats requires the presence of intact Pol I machinery (including UAF). The same is true for silencing of transcription of the native rRNA genes by Pol II, as is evident from polymerase switch in UAF mutants mentioned above. Specific rDNA chromatin structures responsible for the reciprocal relationship in gene expression between Pol I and Pol II are being studied.
Most recently, in order to examine the possibility of coupling of transcription of rRNA with rRNA processing and ribosome assembly, mutants of Pol I were screened for defects in rRNA processing/ribosome assembly. A point mutation was identified in the second largest subunit of Pol I that causes defects in rRNA processing/ribosome assembly in vivo as well as decrease in elongation measured in vitro. Thus, the coupling model has been proven to be correct. It appears that Pol I, elongation factors, and rRNA sequence elements function together to optimize elongation, coordinating cotranscriptional interactions of many factors/snoRNAs with pre-rRNA for correct rRNA processing and ribosome assembly.
Workers in the Nomura laboratory are also studying nuclear and nucleolar structures in connection with Pol I function and ribosome biosynthesis. Transcription of rDNA occurs in the nucleolus. Recent experiments have shown that the presence of Pol I and Pol I-specific transcription factors are important for the maintenance of proper nucleolar structures. Genetic and biochemical approaches combined with cytological analyses are being used in this study. For example, they have discovered that yeast mutants defective in transcription factor UAF give rise to variants able to grow by transcribing endogenous rDNA by RNA polymerase II (Pol II). They have also discovered that the switch to growth using the Pol II system consists of two steps: a mutational alteration in UAF and an expansion of chromosomal rDNA repeats. This phenomenon is being studied in connection with the plasticity of nucleolar structures and its biological significance.
In connection with the above studies, it was shown that silencing of Pol II reporter genes integrated in rDNA repeats requires the presence of intact Pol I machinery (including UAF). The same is true for silencing of transcription of the native rRNA genes by Pol II, as is evident from polymerase switch in UAF mutants mentioned above. Specific rDNA chromatin structures responsible for the reciprocal relationship in gene expression between Pol I and Pol II are being studied.
Most recently, in order to examine the possibility of coupling of transcription of rRNA with rRNA processing and ribosome assembly, mutants of Pol I were screened for defects in rRNA processing/ribosome assembly. A point mutation was identified in the second largest subunit of Pol I that causes defects in rRNA processing/ribosome assembly in vivo as well as decrease in elongation measured in vitro. Thus, the coupling model has been proven to be correct. It appears that Pol I, elongation factors, and rRNA sequence elements function together to optimize elongation, coordinating cotranscriptional interactions of many factors/snoRNAs with pre-rRNA for correct rRNA processing and ribosome assembly.
Publications
Multiprotein transcription factor UAF interacts with the upstream element of yeast RNA polymerase I promoter and forms a stable
preinitiation complex. D.A. Keys, B.-S. Lee, J.A. Dodd, T. T. Nguyen, L. Vu, E. Fantino, L. M. Burson, Y. Nogi, and M. Nomura. Genes & Dev,
10:887-903 (1996).
RRN3 gene of Saccharomyces cerevisiae encodes an essential RNA polymerase I transcription factor which interacts with the
polymerase independently of DNA template. R.T. Yamamoto, Y. Nogi, J.A. Dodd, and M. Nomura. EMBO J. 15: 3964-3973 (1996).
Histones H3 and H4 are components of upstream activation factor (UAF) required for the high level transcription of yeast rDNA by
RNA polymerase I. J. Keener, J.A. Dodd, D. Lalo and M. Nomura. Proc. Natl. Acad. Sci., USA, 94: 13458-13462 (1997).
Mutational analysis of the structure and localization of the nucleolus in the yeast Saccharomyces cerevisiae. M. Oakes, J.P. Aris, J.S.
Brockenbrough, H. Wai, L. Vu and M. Nomura. J. Cell Biol. 143: 23-34 (1998).
Reconstitution of yeast RNA Polymerase I transcription in vitro from purified components: TATA-binding protein is not required for
basal transcription. J. Keener, C.A. Josaitis, J.A. Dodd and M. Nomura. J. Biol Chem, 273:33795-33802 (1998)
RNA polymerase switch in transcription of yeast rDNA: Role of transcription factor UAF (upstream activation factor) in silencing
rDNA transcription by RNA polymerase II. L. Vu, I. Siddiqi, B.-S. Lee, C.A. Josaitis and M. Nomura. Proc Natl Acad Sci USA,
96(8):4390-4395 (1999).
Transcription factor UAF, expansion and contraction of ribosomal DNA (rDNA) repeats, and RNA polymerase switch in
transcription of yeast rDNA. M. Oakes, I. Siddiqi, L. Vu, John Aris and M. Nomura. Mol & Cell Biol, 19: 8559-8569 (1999).
Complete deletion of yeast chromosomal rDNA repeats and integration of a new rDNA repeat: use of rDNA deletion strains for
functional analysis of rDNA promoter elements in vivo. H. Wai, L. Vu, M. Oakes, M. Nomura. Nucleic Acid Res., 28(18): 3524-3534
(2000).
Yeast RNA polymerase I enhancer is dispensable for transcription of chromosomal rDNA and cell growth and its apparent transcription enhancement from ectopic promoters requires Fob1 protein. H. Wai, K. Johzuka, L. Vu, K. Eliason, T. Kobayashi, T. Horiuchi and M. Nomura. Mol. Cell. Biol., 21: 5541-5553 (2001).
Ribosomal RNA gene, RNA polymerases, nucleolar structures, and synthesis of rRNA in the yeast Saccharomyces cerevisiae. M. Nomura, Cold Spring Harbor Symp. Quant. Biol. 66: 555-565 (2001).
Silencing in yeast rDNA chromatin: reciprocal relationship in gene expression between RNA polymerase I and II. F. Cioci, L. Vu, K. Eliason, M. Oakes, I.N. Siddiqi, and M. Nomura. Mol. Cell 12: 135-145 (2003)
SIR2 regulates recombination between different rDNA repeats, but not recombination within individual rRNA genes in yeast. T. Kobayashi, T. Horiuchi, P. Tongaonkar, L. Vu and M. Nomura. Cell 117:441-453 (2004).
RNA Polymerase I remains intact without subunit exchange through multiple rounds of transcription in Saccharomyces cerevisiae. D. Schneider and M. Nomura. Proc. Natl. Acad. Sci. USA 101:15112-15117 (2004).
Histones are required for transcription of yeast rRNA genes by RNA polymerase I. P. Tongaonkar, S.L. French, M.L. Oakes, L. Vu, D.A. Schneider, A.L. Beyer and M. Nomura. Proc. Natl. Acad. Sci. USA 102:10129-10134 (2005).
Role of histone deacetylase Rpd3 in regulating rRNA gene transcription and nucleolar structure in yeast. M.L. Oakes, I. Siddiqi, S.L. French, L. Vu, M. Sato, J.P. Aris, A.L. Beyer and M. Nomura. Mol. Cell. Biol. 26:3889-3901 (2006).
Expression of rRNA genes and nucleolus formation at ectopic chromosomal sites in the yeast Saccharomyces cerevisiae. M.L. Oakes, K. Johzuka, L. Vu, K. Eliason and M. Nomura. Mol. Cell. Biol. 26:6223-6238 (2006).
RNA polymerase II elongation factors Spt4p and Spt5p play roles in transcription elongation by RNA polymerase I and rRNA processing. D. Schneider, S.L. French, Y.N. Osheim, A.O. Bailey, L. Vu, J. Dodd, J.R. Yates, A.L. Beyer and M. Nomura. Proc. Natl. Acad. Sci. USA 103:12707-12712 (2006).
Transcription elongation by RNA polymerase I is linked to efficient rRNA processing and ribosome assembly. D.A. Schneider, A. Michel, M.L. Sikes, L. Vu, J.A. Dodd, S. Salgia, Y.N. Osheim, A.L. Beyer and M. Nomura. Mol. Cell, 26:217-229 (2007).
Visual Analysis of the Yeast 5S rRNA Gene Transcriptome: Regulation and Role of La Protein. S.L. French, Y.N. Osheim, D.A. Schneider, M.L. Sikes, C.F. Fernandez, L.A. Copela, V.A. Misra, M. Nomura, S.L. Wolin, and A.L. Beyer. Mol. Cell. Biol. 28:4576-4587 (2008).
Professional Societies
American Academy of Arts and Science
National Academy of Sciences
Graduate Programs
Cell Biology
Mechanisms of Gene Expression
Link to this profile
https://faculty.uci.edu/profile/?facultyId=2259
https://faculty.uci.edu/profile/?facultyId=2259
Last updated
07/11/2008
07/11/2008