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Professional Preparation
Ph.D. - Microbiology and Molecular Genetics University of Medicine and Dentistry of New Jersey/ Rutgers University - 1985
M.S. - Biology Seton Hall University - 1979
B.S. - Biology/Medical Technology Seton Hall University - 1976
Research Areas
Research Interests
Translational Regulation in Yeast
Protein synthesis in eukaryotic organisms is a complex
process that requires cooperation among a large number of polypeptides
including ribosomal proteins, modification enzymes, and
ribosome-associated translation factors. Our research focuses on the
initiation phase of protein synthesis, during which ribosomes select
mRNAs to be translated and identify the translational start site. This
process requires a set of eukaryotic translation initiation
factors (eIFs), many of which are comprised of multiple
polypeptide subunits (Fig. 1). Initiation factors, as well as the
overall pathway for initiation of protein synthesis, appear to be
conserved between eukaryotes as widely divergent as yeasts and humans.
In fact, a number of yeast initiation factors have been shown to
substitute in in vitro initiation reactions using otherwise mammalian
components, while a number of mammalian genes encoding initiation factor
subunits have been shown to substitute in vivo for their yeast
counterparts. Because of the ability to combine powerful genetic
approaches with biochemical analyses, we use the yeast Saccharomyces
cerevisiae as a model system to dissect the complexities of
eukaryotic protein synthesis.
One area of current research is eIF2 and its guanine
nucleotide exchange factor eIF2B. eIF2 is a heterotrimeric GTP-binding
protein whose known functions include delivery of charged initiator
methionyl-tRNA to the ribosome, as well as a role in identifying the
translational start site. The three eIF2 subunits are encoded by
essential genes (a, SUI2; b, SUI3; g, GCD11).
eIF2B is a heteropentamer, and four of the five corresponding
structural genes (GCD1, GCD2, GCD6, and GCD7)
are essential in yeast.
Although we understand something of the overall function of
these two translation factors, less is known about the function of
individual subunits within these macromolecular complexes. It is
important to identify these functions, particularly since altered
regulation of eIF2 and eIF2B function has been shown to result in
malignant transformation in mammalian systems.
Earlier work from our lab lead to the initial report
describing a structural gene encoding a g-subunit of eIF2, the GCD11
gene in S. cerevisiae. Clues to the function of eIF2g can be
found in its deduced amino acid sequence, which bears remarkable
similarity to prokaryotic and mitochondrial EF-Tu proteins. EF-Tu binds
charged elongator tRNAs in a GTP-dependent fashion, and is the
prototypical member of the GTP-binding family of translational factors.
The sequence similarity between eIF2g and EF-Tu proteins apparently
reflects functional similarities, as genetic and biochemical studies
from our lab (Erickson and Hannig, 1996) indicate that the g subunit
plays a major role in ligand-binding by eIF2 (i.e., binding guanine
nucleotides and charged initiator methionyl-tRNA). Biochemical analysis
of additional eIF2 complexes containing alterations in the g subunit (as
well as the a and b subunits) may reveal subunit functions that lie
downstream from ligand-binding in the initiation pathway.
We are also examining interactions between eIF2 and eIF2B.
Considerable interest exists in eIF2B because it is the most complex
guanine nucleotide exchange factor currently known. The reasons for this
complexity are not clear, but may reflect different catalytic and/or
regulatory functions for individual subunits. We recently identified
conditions that appear to reduce the requirement for eIF2B in yeast.
Analysis of these mutants and additional partial loss-of-function
mutations should allow us to address the role(s) of individual subunits
in eIF2B function, and thereby gain a more complete understanding of
this complex exchange factor.
Publications
Singh, C. R., Curtis, C., Yamamoto, Y., Hall, N. S., Kruse, D. S., He, H., Hannig, E. M., and Asano, K. 2005. e1F5 is critical for integrity of scanning preinitiation complex and accurate control of GCN4 translation. Mol. Cell Biol., 25: 5480-5491. 2005 - Publication
Yamamoto, Y., Singh, C. R., Marintchev, A., Hall, N. S., Hannig, E. M., Wagner, G., and Asano, K. 2005. The e1F5 AA-box domain has two distinct interfaces for multifactor assembly and scanning. Proc.Natl. Acad. Sci. USA, 102: 16164-16169. 2005 - Publication
Asano, K., Phan, L., Krishnamoorthy, T., Pavitt, G.D., Gomez, E., Hannig, E.M., Nika, J., Donahue, T.F., Huang, H.-k., and Hinnebusch, A.G. 2002. Analysis and reconstitution of translation initiation in vitro. Meth. Enzymol., 351, 221-247. 2002 - Publication
Erickson, F.L., Nika, J., Rippel, S., and Hannig, E.M. 2001. Minimum requirements for the function of eukaryotic translation initiation factor 2. Genetics, 158, 123-132. 2001 - Publication
Nika, J., Rippel, S., and Hannig, E.M. 2001. Biochemical analysis of the eIF2 By complex reveals a structural function for eIF2ot in catalyzed nucleotide exchange. J Biol. Chem., 276, 1051-1056. 2001 - Publication
Nika, J., Yang, W., Pavitt, G., Hinnebusch, A.G., and Hannig, E.M. 2000. Purification and kinetic analysis of eIF2B from Saccharomyces cerevisiae. J Biol. Chem., 275, 26011-26017. 2000 - Publication
Astrom, S.U., Nordlund, M., Erickson, F.L., Hannig, E.M. and Bystrom, A.S. 1999. Modification of adenosine 64 of the yeast initiator tRNA is required for optimal tRNAiMet:GTP:e1F -2 ternary complex interactions. Mol. Gen. Genet., 261, 967-976. 1999 - Publication
Huang, H., Yoon, H., Hannig, E.M., and Donahue, T.F. 1997. GTP hydrolysis controls stringent selection of the AUG start codon during translation initiation in Saccharomyces cerevisiae. Genes Devel., 11, 2396-24 1 3 . 1997 - Publication
Appointments
Associate Professor The University of Texas at Dallas [1996–Present]
Assistant Professor The University of Texas at Dallas [1990–1996]
Predoctoral Trainee Rutgers Medical School [1982–1985]
Medical Technologist (ASCP) College Hospital/UMDNJ, Newark, New Jersey [1976–1982]
Division of Clinical Microbiology
Additional Information
Honors and Awards
1987-1990 Intramural Research Training Award, NIH
1985-1987 Postdoctoral Fellowship, American Cancer Society
1984 Graduate Student Scholarship, Theobald Smith Society, New Jersey Branch, ASM
1982 Graduate Student Scholarship, New York City Branch, ASM
Professional Memberships
American Society for Biochemistry and Molecular Biology
Genetics Society of America
Professional Activities
Member, Genetic Mechanisms of Cancer Study Section, American Cancer Society (1997-2000)
Reviewer (grants) (ad hoc), Wellcome Foundation (Great Britain)
Reviewer (grants) (ad hoc), National Science Foundation, Molecular Biochemistry Study Section
Reviewer (grants) (ad hoc), Austrian Science Foundation (Fonds zur Foderung der wissenschaitlichen Forschung)
Reviewer (grants) (ad hoc) K-INBRE Pilot Grant Program
Reviewer (journal), Molecular and Cell Biology
Reviewer (journal), Molecular and Cellular Biochemistry
Reviewer (journal), Molecular Biology and Evolution
Reviewer (journal), Gene
Reviewer (journal), Genetics
Reviewer (journal), Journal of Biological Chemistry
Reviewer (textbook) Weaver, R.F. and Hedrick, P.W., Genetics, 3rd edition. Wm. C. Brown, publisher
Reviewer (textbook) Lewin, B. Genes VIII. Oxford University Press, publisher
Reviewer (textbook) Cappucino, J. G., and Sherman, N. Microbiology: A Laboratory Manual, 7th ed.(8th ed) Benjamin Cummings, publisher
Reviewer (textbook) Madigan, M. T. et al. Brock Biology of Microorganisms, 10th ed. Prentice Hall, publisher
Reviewer (textbook) Madigan, M. T. et al. Brock Biology of Microorganisms, ll"` ed. Prentice Hall, publisher (published in 2005).
Reviewer (textbook) Russell, Peter. iGenetics: a Mendelian Approach. Pearson Benjamin Cummings, San Francisco, publisher (published in 2005).
Test Bank Author for Russell, Peter. iGenetics: a Mendelian Approach. Pearson Benjamin Cummings, San Francisco, publisher (published in 2005)
Affiliations
Students Graduated
XioFeng Yang (M.S., May, 1994) Thesis: "Molecular modeling of the y-subunit of eukaryotic initiation factor 2 (elF2) from Saccharomyces cerevisiae". Current position: Postdoctoral Fellow/Research Scientist, Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX.
David Dorris (Ph.D., August, 1994) Thesis: "Characterization of mutations that alter the function of eIF2y in the yeast Saccharomyces cerevisiae". Current position: Director, RNA Interference Technologies, Ambion, Inc., Austin, TX.
F. Les Erickson (Ph.D., December, 1996) Thesis: "Functional analysis of eIF2y and its interactions with ligands and e1F2B". Current position: Assistant Professor, Department of Biological Sciences, Salisbury University, Salisbury, MD.
Joseph Nika (Ph.D., August, 1999) Thesis: "Characterization of the eIF2 guanine nucleotide exchange
reaction". Current position: Assistant Professor and Health Professions Advisor, University of Nevada at Las Vegas, Las Vegas, NV.
Scott Rippel (Ph.D. August, 1999) Thesis: "Analysis of e1F 2 and it role in delivery of Met-tRNAiMet to the correct translational start site". Current position: Senior Lecturer, Department of Molecular and Cell Biology, The University of Texas at Dallas, Richardson, TX.
Funding
Translational Regulation in Yeast
$270,000 - American Cancer Society [1997–2001]
Translational Regulation in Yeast
$60,000 - National Science Foundation [1996–1997]
Molecular and Cell Biology Program, The University of Texas at Dallas
$5,000 - Institutional BRSG [1992–1993]
Translational Regulation in Yeast
$285,000 - National Science Foundation [1991–1995]
Molecular and Cell Biology Program, The University of Texas at Dallas