Abstract

The cap structure and the poly(A) tail on messenger RNA (mRNA) work together to stimulate translation initiation in yeast through their interaction with the translation initiation factor eIF4G. The cap binding protein eIF4E and the poly(A) tail binding protein Pab1p mediate the interaction of eIF4G with each of these mRNA structures. The RNA- activated ATPase eIF4A also interacts with eIF4G. This proposal outlines experiments whose goals are to understand how each of these proteins as well as RNA interacts with yeast eIF4G1 and with each other. Another goal is to understand whether eIF4A enzymatic activity or the association of the ribosome bound initiation factor eIF3 with eIF4G1 is stimulated when mRNA is circularized through the interaction of eIF4E and Pab1p with eIF4G1. A final goal of these experiments is to identify and then characterize other yeast proteins which either activate or repress the function of eIF4G1 and its associated proteins. Our results should help to elucidate the mechanisms by which translation initiation is stimulated and regulated in eucaryotes. This information will be invaluable in understanding alterations to the translational apparatus resulting from some types of cellular transformations or viral infections, and in developing assays and then compounds which will provide therapeutic options to correcting these alterations.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM050308-08
Application #
6385847
Study Section
Molecular Biology Study Section (MBY)
Program Officer
Rhoades, Marcus M
Project Start
1994-09-01
Project End
2003-08-31
Budget Start
2001-09-01
Budget End
2003-08-31
Support Year
8
Fiscal Year
2001
Total Cost
$275,182
Indirect Cost

  Institution

Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704

  Publications

Holmes, L E A; Campbell, S G; De Long, S K et al. (2004) Loss of translational control in yeast compromised for the major mRNA decay pathway. Mol Cell Biol 24:2998-3010
Inada, Toshifumi; Winstall, Eric; Tarun Jr, Salvador Z et al. (2002) One-step affinity purification of the yeast ribosome and its associated proteins and mRNAs. RNA 8:948-58
Ashe, M P; Slaven, J W; De Long, S K et al. (2001) A novel eIF2B-dependent mechanism of translational control in yeast as a response to fusel alcohols. EMBO J 20:6464-74
Winstall, E; Sadowski, M; Kuhn, U et al. (2000) The Saccharomyces cerevisiae RNA-binding protein Rbp29 functions in cytoplasmic mRNA metabolism. J Biol Chem 275:21817-26
Fortes, P; Inada, T; Preiss, T et al. (2000) The yeast nuclear cap binding complex can interact with translation factor eIF4G and mediate translation initiation. Mol Cell 6:191-6
Ashe, M P; De Long, S K; Sachs, A B (2000) Glucose depletion rapidly inhibits translation initiation in yeast. Mol Biol Cell 11:833-48
Morrissey, J P; Deardorff, J A; Hebron, C et al. (1999) Decapping of stabilized, polyadenylated mRNA in yeast pab1 mutants. Yeast 15:687-702
Tarun Jr, S Z; Sachs, A B (1997) Binding of eukaryotic translation initiation factor 4E (eIF4E) to eIF4G represses translation of uncapped mRNA. Mol Cell Biol 17:6876-86
Deardorff, J A; Sachs, A B (1997) Differential effects of aromatic and charged residue substitutions in the RNA binding domains of the yeast poly(A)-binding protein. J Mol Biol 269:67-81
Tarun Jr, S Z; Sachs, A B (1996) Association of the yeast poly(A) tail binding protein with translation initiation factor eIF-4G. EMBO J 15:7168-77

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