Masayasu Nomura
Grace Bell Professor of Biological Chemistry
Ph.D., University of Tokyo, 1957
University of California, Irvine
Department of Biological Chemistry
Irvine, CA 92697-1700
Office: (949) 824-4673
mnomura@uci.edu
UCI Faculty Profile: Masayasu Nomura
Photos from the International Nomura Symposium
April 19-20, 2007
Ribosomes: From Structure to Gene Expression and Beyond
If you are interested in a postdoctoral scholar
position in the Nomura Lab, please see information on UCI's academic
employment website:
http://www.eod.uci.edu/ads/index_other.php#3704
Research Interests:
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.
Masayasu Nomura Laboratory Members:
- M. Nomura
- Principal Investigator
- Melanie Oakes
- Associate Specialist
- Jonathan Dodd
- Senior Research Associate
- Loan Vu
- Senior Research Associate
- Qais Al-Hadid
- Staff Research Associate
Selected Publications:
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).
List of Publications via PubMed (NIH National Library of Medicine)
