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Molecular and Cellular Biology, August 1999, p. 5257-5266, Vol. 19, No. 8
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Mutations in Elongation Factor 1beta , a Guanine Nucleotide Exchange Factor, Enhance Translational Fidelity

Anne Carr-Schmid,1 Louis Valente,1 Valerie I. Loik,1 Tanishia Williams,1 Lea M. Starita,1 and Terri Goss Kinzy1,2,*

Department of Molecular Genetics and Microbiology, UMDNJ Robert Wood Johnson Medical School,1 and The Cancer Institute of New Jersey,2 Piscataway, New Jersey

Received 8 December 1998/Returned for modification 22 January 1999/Accepted 18 May 1999

Translation elongation factor 1beta (EF-1beta ) is a member of the family of guanine nucleotide exchange factors, proteins whose activities are important for the regulation of G proteins critical to many cellular processes. EF-1beta is a highly conserved protein that catalyzes the exchange of bound GDP for GTP on EF-1alpha , a required step to ensure continued protein synthesis. In this work, we demonstrate that the highly conserved C-terminal region of Saccharomyces cerevisiae EF-1beta is sufficient for normal cell growth. This region of yeast and metazoan EF-1beta and the metazoan EF-1beta -like protein EF-1delta is highly conserved. Human EF-1beta , but not human EF-1delta , is functional in place of yeast EF-1beta , even though both EF-1beta and EF-1delta have previously been shown to have guanine nucleotide exchange activity in vitro. Based on the sequence and functional homology, mutagenesis of two C-terminal residues identical in all EF-1beta protein sequences was performed, resulting in mutants with growth defects and sensitivity to translation inhibitors. These mutants also enhance translational fidelity at nonsense codons, which correlates with a reduction in total protein synthesis. These results indicate the critical function of EF-1beta in regulating EF-1alpha activity, cell growth, translation rates, and translational fidelity.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, UMDNJ Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854-5635. Phone: (732) 235-5450. Fax: (732) 235-5223. E-mail: kinzytg{at}umdnj.edu.

Molecular and Cellular Biology, August 1999, p. 5257-5266, Vol. 19, No. 8
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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