HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 16, 15601-15611, April 22, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/16/15601    most recent M413728200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Komar, A. A. Articles by Merrick, W. C. Search for Related Content PubMed PubMed Citation Articles by Komar, A. A. Articles by Merrick, W. C. Social Bookmarking                      What's this?

Novel Characteristics of the Biological Properties of the Yeast Saccharomyces cerevisiae Eukaryotic Initiation Factor 2A^*

Anton A. Komar, Stephane R. Gross, Diane Barth-Baus¶, Ryan Strachan, Jack O. Hensold¶, Terri Goss Kinzy, and William C. Merrick||

From the Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, the Department of Molecular Genetics, Microbiology, and Immunology, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, and the ^¶Veterans Affairs Medical Center and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106

Eukaryotic initiation factor 2A (eIF2A) has been shown to direct binding of the initiator methionyl-tRNA (Met-tRNA_i) to 40 S ribosomal subunits in a codon-dependent manner, in contrast to eIF2, which requires GTP but not the AUG codon to bind initiator tRNA to 40 S subunits. We show here that yeast eIF2A genetically interacts with initiation factor eIF4E, suggesting that both proteins function in the same pathway. The double eIF2A/eIF4E-ts mutant strain displays a severe slow growth phenotype, which correlated with the accumulation of 85% of the double mutant cells arrested at the G₂/M border. These cells also exhibited a disorganized actin cytoskeleton and elevated actin levels, suggesting that eIF2A might be involved in controlling the expression of genes involved in morphogenic processes. Further insights into eIF2A function were gained from the studies of eIF2A distribution in ribosomal fractions obtained from either an eIF5B (fun12) strain or a eIF3b-ts (prt1-1) strain. It was found that the binding of eIF2A to 40 and 80 S ribosomes was not impaired in either strain. We also found that eIF2A functions as a suppressor of Ure2p internal ribosome entry site-mediated translation in yeast cells. The regulation of expression from the URE2 internal ribosome entry site appears to be through the levels of eIF2A protein, which has been found to be inherently unstable with a half-life of 17 min. It was hypothesized that this instability allows for translational control through the level of eIF2A protein in yeast cells.

Received for publication, December 6, 2004 , and in revised form, February 1, 2005.

^* This work was supported by NIGMS, National Institutes of Health (NIH), Grants GM26796 and GM68079 (to W. C. M.), NIDDK, NIH, Grant DK43414 (to J. O. H.), and NIH Grant GM62789 (to T. G. K. and S. R. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed: Dept. of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106. Tel.: 216-368-3578; Fax: 216-368-3419; E-mail: wcm2{at}cwru.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. C. Reineke, A. A. Komar, M. G. Caprara, and W. C. Merrick A Small Stem Loop Element Directs Internal Initiation of the URE2 Internal Ribosome Entry Site in Saccharomyces cerevisiae J. Biol. Chem., July 4, 2008; 283(27): 19011 - 19025. [Abstract] [Full Text] [PDF]

				V. V. Zeenko, C. Wang, M. Majumder, A. A. Komar, M. D. Snider, W. C. Merrick, R. J. Kaufman, and M. Hatzoglou An efficient in vitro translation system from mammalian cells lacking the translational inhibition caused by eIF2 phosphorylation RNA, March 1, 2008; 14(3): 593 - 602. [Abstract] [Full Text] [PDF]

				O. Galkin, A. A. Bentley, S. Gupta, B.-A. Compton, B. Mazumder, T. G. Kinzy, W. C. Merrick, M. Hatzoglou, T. V. Pestova, C. U.T. Hellen, et al. Roles of the negatively charged N-terminal extension of Saccharomyces cerevisiae ribosomal protein S5 revealed by characterization of a yeast strain containing human ribosomal protein S5 RNA, December 1, 2007; 13(12): 2116 - 2128. [Abstract] [Full Text] [PDF]

				F. Robert, L. D. Kapp, S. N. Khan, M. G. Acker, S. Kolitz, S. Kazemi, R. J. Kaufman, W. C. Merrick, A. E. Koromilas, J. R. Lorsch, et al. Initiation of Protein Synthesis by Hepatitis C Virus Is Refractory to Reduced eIF2 {middle dot} GTP {middle dot} Met-tRNAiMet Ternary Complex Availability Mol. Biol. Cell, November 1, 2006; 17(11): 4632 - 4644. [Abstract] [Full Text] [PDF]

				I. Ventoso, M. A. Sanz, S. Molina, J. J. Berlanga, L. Carrasco, and M. Esteban Translational resistance of late alphavirus mRNA to eIF2{alpha} phosphorylation: a strategy to overcome the antiviral effect of protein kinase PKR Genes & Dev., January 1, 2006; 20(1): 87 - 100. [Abstract] [Full Text] [PDF]