Intracellular translation initiation factor levels in Saccharomyces cerevisiae and their role in cap‐complex function
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Summary: Knowledge of the balance of activities of eukaryotic initiation factors (eIFs) is critical to our understanding of the mechanisms underlying translational control. We have therefore estimated the intracellular levels of 11 eIFs in logarithmically growing cells of Saccharomyces cerevisiae using polyclonal antibodies raised in rabbits against recombinant proteins. Those factors involved in 43S complex formation occur at levels comparable (i.e. within a 0.5‐ to 2.0‐fold range) to those published for ribosomes. In contrast, the subunits of the cap‐binding complex eIF4F showed considerable variation in their abundance. The helicase eIF4A was the most abundant eIF of the yeast cell, followed by eIF4E at multiple copies per ribosome, and eIF4B at approximately one copy per ribosome. The adaptor protein eIF4G was the least abundant of the eIF4 factors, with a copy number per cell that is substoichiometric to the ribosome and similar to the abundance of mRNA. The observed excess of eIF4E over its functional partner eIF4G is not strictly required during exponential growth: at eIF4E levels artificially reduced to 30% of those in wild‐type yeast, growth rates and the capacity for general protein synthesis are only minimally affected. This demonstrates that eIF4E does not exercise a higher level of rate control over translation than other eIFs. However, other features of the yeast life cycle, such as the control of cell size, are more sensitive to changes in eIF4E abundance. Overall, these data constitute an important basis for developing a quantitative model of the workings of the eukaryotic translation apparatus.
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SCM protein levels sum to just over 35 million protein molecules per haploid cell, similar to the 50 million molecules per cell estimated previously within the variation in total protein extraction.
“Scaled to 4μg of protein in 1.5×106 cells (2.7pg protein per yeast cell in cells roughly 30 μm 3 in size) [55], SCM protein levels sum to just over 35 million protein molecules per haploid cell, similar to the 50 million molecules per cell estimated previously [20] within the variation in total protein extraction from haploid yeast cells (cf. [56], which estimates 4.95pg per cell).”
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Cites
Mathews, D. H., Sabina, J., Zuker, M., & Turner, D. H. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.2700 · Cited by 3,795 · see citing works
The scanning model for translation: an update.
Kozak, M. (1989) · The Journal of Cell Biology · doi:10.1083/jcb.108.2.229 · Cited by 3,485 · see citing works
The economics of ribosome biosynthesis in yeast
Warner, J. R. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(99)01460-7 · Cited by 1,933 · see citing works
The Transcriptional Program of Sporulation in Budding Yeast
Chu, S., DeRisi, J. L., Eisen, M. B., Mulholland, J., Botstein, D., Brown, P. O., & Herskowitz, I. (1998) · Science · doi:10.1126/science.282.5389.699 · Cited by 1,860 · see citing works
Dissecting the regulatory circuitry of a eukaryotic genome
Holstege, F. C. P., Jennings, E. G., Wyrick, J. J., Lee, T. I., Hengartner, C. J., Green, M. R., Golub, T. R., Lander, E. S., & Young, R. A. (1998) · Cell · doi:10.1016/s0092-8674(00)81641-4 · Cited by 1,670 · see citing works
Zimmerman, S. B., & Trach, S. O. (1991) · Journal of Molecular Biology · doi:10.1016/0022-2836(91)90499-v · Cited by 1,337 · see citing works
Translational control of gene expression
Hannig, E. M. (2001) · BioEssays · doi:10.1002/bies.1108 · Cited by 1,194 · see citing works
How do eucaryotic ribosomes select initiation regions in messenger RNA?
Kozak, M. (1978) · Cell · doi:10.1016/0092-8674(78)90039-9 · Cited by 833 · see citing works
Molecular mechanisms of translation initiation in eukaryotes
Pestova, T. V., KOLUPAEVA, V. G., Lomakin, I. B., Pilipenko, E. V., Shatsky, I. N., Agol, V. I., & Hellen, C. U. T. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111145798 · Cited by 742 · see citing works
Association of the yeast poly(A) tail binding protein with translation initiation factor eIF‐4G.
Tarun, S. Z., & Sachs, A. B. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01108.x · Cited by 690 · see citing works
Bidirectional RNA Helicase Activity of Eucaryotic Translation Initiation Factors 4A and 4F
Rozen, F., Edery, I., Meerovitch, K., Dever, T. E., Merrick, W. C., & Sonenberg, N. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.3.1134 · Cited by 632 · see citing works
Haghighat, A., Mader, S., Pause, A., & Sonenberg, N. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00257.x · Cited by 615 · see citing works
A Sampling of the Yeast Proteome
Futcher, B., Latter, G. I., Monardo, P., McLaughlin, C. S., & Garrels, J. I. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.11.7357 · Cited by 606 · see citing works
Etchison, D., Milburn, S. C., Edery, I., Sonenberg, N., & Hershey, J. W. B. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)33352-0 · Cited by 583 · see citing works
Unwinding RNA in Saccharomyces cerevisiae: DEAD-box proteins and related families
de la Cruz, J., Kressler, D., & Linder, P. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(99)01376-6 · Cited by 534 · see citing works
Translational Regulation of Yeast GCN4
Hinnebusch, A. G. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.35.21661 · Cited by 526 · see citing works
Duncan, R., Milburn, S. C., & Hershey, J. W. B. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)75938-9 · Cited by 483 · see citing works
Glucose Depletion Rapidly Inhibits Translation Initiation in Yeast
Ashe, M., Long, S. K. D., & Sachs, A. B. (2000) · Molecular Biology of the Cell · doi:10.1091/mbc.11.3.833 · Cited by 441 · see citing works
The joining of ribosomal subunits in eukaryotes requires eIF5B
Pestova, T., Lomakin, I., Lee, J.-H., Choi, S. K., Dever, T., & Hellen, C. (2000) · Nature · doi:10.1038/35002118 · Cited by 433 · see citing works
Pause, A., Méthot, N., Svitkin, Y. V., Merrick, W. C., & Sonenberg, N. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06370.x · Cited by 393 · see citing works
Eukaryotic initiation factor eIF2
Kimball, S. R. (1999) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(98)00128-9 · Cited by 344 · see citing works
Candida rugosa lipases: Molecular biology and versatility in biotechnology
Benjamin, S., & Pandey, A. (1998) · Yeast · doi:10.1002/(sici)1097-0061(19980915)14:12 · Cited by 304 · see citing works
Asano, K., Clayton, J., Shalev, A., & Hinnebusch, A. G. (2000) · Genes & Development · doi:10.1101/gad.831800 · Cited by 302 · see citing works
Donahue, T. F., Cigan, A. M., Pabich, E. K., & Castilho, B. A. (1988) · Cell · doi:10.1016/s0092-8674(88)80006-0 · Cited by 267 · see citing works
Steinberg, T. H., Jones, L. J., Haugland, R. P., et al. (1996) · Analytical Biochemistry · doi:10.1006/abio.1996.0319 · Cited by 262 · see citing works
Pavitt, G. D., Ramaiah, K. V. A., Kimball, S. R., & Hinnebusch, A. G. (1998) · Genes & Development · doi:10.1101/gad.12.4.514 · Cited by 256 · see citing works
Posttranscriptional Control of Gene Expression in Yeast
McCarthy, J. E. G. (1998) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.62.4.1492-1553.1998 · Cited by 228 · see citing works
Self-citation2 The Pathway and Mechanism of Eukaryotic Protein SynthesisPreprint
Merrick, W. C., & Hershey, J. W. B. (1996) · Cold Spring Harbor Monograph Archive · doi:10.1101/087969458.30.31 · Cited by 221 · see citing works
de la Cruz, J., Iost, I., Kressler, D., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.10.5201 · Cited by 215 · see citing works
Translation initiation requires the PAB-dependent poly(A) ribonuclease in yeast
Sachs, A. B., & Deardorff, J. A. (1992) · Cell · doi:10.1016/0092-8674(92)90246-9 · Cited by 214 · see citing works
Duncan, R., & Hershey, J. W. B. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)32356-1 · Cited by 195 · see citing works
Phan, L. D., Zhang, X., Asano, K., et al. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.8.4935 · Cited by 193 · see citing works
Dependency of size of Saccharomyces cerevisiae cells on growth rate
TYSON, C. B., Lord, P. G., & Wheals, A. E. (1979) · Journal of Bacteriology · doi:10.1128/jb.138.1.92-98.1979 · Cited by 187 · see citing works
Goyer, C., Altmann, M., Lee, H. S., Blanc, A., Deshmukh, M., Woolford, J. L., Trachsel, H., & Sonenberg, N. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.8.4860 · Cited by 183 · see citing works
Altmann, M., Schmitz, N., Berset, C., et al. (1997) · The EMBO Journal · doi:10.1093/emboj/16.5.1114 · Cited by 173 · see citing works
Yoon, H.-J., & Donahue, T. F. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.1.248 · Cited by 170 · see citing works
Flynn, A., & Proud, C. G. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.37.21684 · Cited by 152 · see citing works
Asano, K., Phan, L. D., Anderson, J. T., & Hinnebusch, A. G. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.29.18573 · Cited by 146 · see citing works
Stabilization of Eukaryotic Initiation Factor 4E Binding to the mRNA 5′-Cap by Domains of eIF4G
von der Haar, T., Ball, P. D., & McCarthy, J. E. G. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004565200 · Cited by 146 · see citing works
Self-citationPtushkina, M., von der Haar, T., Vasilescu, S., Frank, R., Birkenhäger, R., & McCarthy, J. E. G. (1998) · The EMBO Journal · doi:10.1093/emboj/17.16.4798 · Cited by 144 · see citing works
Self-citationRau, M., Ohlmann, T., Morley, S., & Pain, V. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.15.8983 · Cited by 141 · see citing works
The p46 subunit of eukaryotic initiation factor (eIF)-4F exchanges with eIF-4A.
Yoder-Hill, J., Pause, A., Sonenberg, N., & Merrick, W. C. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53358-5 · Cited by 140 · see citing works
Altmann, M., Handschin, C., & Trachsel, H. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.3.998-1003.1987 · Cited by 130 · see citing works
The emerging roles of translation factor eIF4E in the nucleus
Strudwick, S., & Borden, K. L. B. (2002) · Differentiation · doi:10.1046/j.1432-0436.2002.700102.x · Cited by 129 · see citing works
Protein based microarrays: A tool for probing the proteome of cancer cells and tissues
Madoz‐Gúrpide, J., Wang, H., Misek, D. E., Brichory, F., & Hanash, S. (2001) · PROTEOMICS · doi:10.1002/1615-9861(200110)1:10 · Cited by 122 · see citing works
Korneeva, N. L., Lamphear, B. J., Hennigan, F. L. C., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m007525200 · Cited by 120 · see citing works
Chaudhuri, J., Chowdhury, D., & Maitra, U. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.25.17975 · Cited by 107 · see citing works
A new yeast translation initiation factor suppresses a mutation in the eIF‐4A RNA helicase.
Coppolecchia, R., Buser, P., Stotz, A., et al. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb06078.x · Cited by 106 · see citing works
Browning, K. S., Gallie, D., Hershey, J. W. B., Hinnebusch, A. G., Maitra, U., Merrick, W. C., & Norbury, C. J. (2001) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(01)01825-4 · Cited by 100 · see citing works
Chaudhuri, J., Si, K., & Maitra, U. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.12.7883 · Cited by 96 · see citing works
Altmann, M., Handschin, C., & Trachsel, H. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.3.998 · Cited by 94 · see citing works
Eukaryotic initiation factor 2B (eIF2B)
Webb, B. L. J., & Proud, C. G. (1997) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(97)00039-3 · Cited by 92 · see citing works
Vilela, C., Velasco, C., Ptushkina, M., et al. (2000) · The EMBO Journal · doi:10.1093/emboj/19.16.4372 · Cited by 88 · see citing works
Lang, V., Zanchin, N. I. T., Lünsdorf, H., et al. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37577-4 · Cited by 83 · see citing works
Translation initiation and its deregulation during tumorigenesis
Watkins, S. J., & Norbury, C. J. (2002) · British Journal of Cancer · doi:10.1038/sj.bjc.6600222 · Cited by 70 · see citing works
The influence of 5'-secondary structures upon ribosome binding to mRNA during translation in yeast.
Sagliocco, F. A., Laso, M. R. V., Zhu, D., Tuite, M. F., McCarthy, J. E. G., & Brown, A. J. P. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)74344-0 · Cited by 69 · see citing works
Self-citationNeff, C., & Sachs, A. B. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.8.5557 · Cited by 65 · see citing works
Dombek, K. M., & Ingram, L. O. (1986) · Applied and Environmental Microbiology · doi:10.1128/aem.51.1.197-200.1986 · Cited by 63 · see citing works
Iron regulation of ferritin gene expression
Munro, H. N. (1990) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240440205 · Cited by 58 · see citing works
Zanchin, N. I. T., & McCarthy, J. E. G. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.44.26505 · Cited by 57 · see citing works
Self-citationA deletion mutant of L-A double-stranded RNA replicates like M1 double-stranded RNA
Esteban, R., & Wickner, R. B. (1988) · Journal of Virology · doi:10.1128/jvi.62.4.1278-1285.1988 · Cited by 54 · see citing works
Modulation of Eukaryotic mRNA Stability via the Cap-binding Translation Complex eIF4F
Ramirez, C. V., Vilela, C., Berthelot, K., et al. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00162-6 · Cited by 54 · see citing works
Danaie, P., Altmann, M., Hall, M. N., et al. (1999) · Biochemical Journal · doi:10.1042/bj3400135 · Cited by 52 · see citing works
Das, S., & Maitra, U. (2001) · Progress in nucleic acid research and molecular biology · doi:10.1016/s0079-6603(01)70018-9 · Cited by 48 · see citing works
Vasilescu, S., Ptushkina, M., Linz, B., et al. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.12.7030 · Cited by 47 · see citing works
Ribosome recruitment and scanning: what’s new?
Pestova, T. V., & Hellen, C. U. T. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(99)01356-0 · Cited by 45 · see citing works
Altmann, M., Krieger, M., & Trachsel, H. (1989) · Nucleic Acids Research · doi:10.1093/nar/17.18.7520 · Cited by 28 · see citing works
Etchison, D. O., & Milburn, S. C. (1987) · Molecular and Cellular Biochemistry · doi:10.1007/bf00219394 · Cited by 25 · see citing works
Russo, G. L., BOS, C. V. D., Sutton, A., et al. (2000) · Biochemical Journal · doi:10.1042/0264-6021:3510143 · Cited by 19 · see citing works
Langlands, K., & Prochownik, E. V. (1997) · Analytical Biochemistry · doi:10.1006/abio.1997.2184 · Cited by 17 · see citing works
Translation initiation and surface plasmon resonance: new technology applied to old questions
von der Haar, T., Hughes, J. M. X., Karim, M. M., et al. (2002) · Biochemical Society Transactions · doi:10.1042/bst0300155 · Cited by 13 · see citing works
Danaie, P., Altmann, M., Hall, M. N., et al. (1999) · Biochemical Journal · doi:10.1042/0264-6021:3400135 · Cited by 10 · see citing works
Russo, G. L., BOS, C. V. D., & Marshak, D. R. (2001) · Molecular and Cellular Biochemistry · doi:10.1023/a:1013189629207 · Cited by 9 · see citing works
Russo, G. L., BOS, C. V. D., & Marshak, D. R. (2001) · Springer eBooks · doi:10.1007/978-1-4615-1723-8_14 · Cited by 7 · see citing works
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Suzuki, C., Garces, R. G., Edmonds, K. A., Hiller, S., Hyberts, S. G., Marintchev, A., & Wagner, G. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712235105 · Cited by 165 · see citing works
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- Authors
- von der Haar, T., & McCarthy, J. E. G.
- Affiliations
- University of Manchester (GB)
- ORCID
- McCarthy, John E. G.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2002-10
- Volume
- 46
- Issue
- 2
- Pages
- 531-544
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W2132432514
- Cited by
- 137
- References
- 74
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 7 · 2022: 8 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 6 · 2017: 3 · 2016: 3 · 2015: 4 · 2014: 6 · 2013: 6 · 2012: 8
- FWCI
- 3.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Kent Academic Repository (University of Kent) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- Wellcome Trust
- National Institutes of Health
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- eukaryotic initiation factors, eIF4E, eIF4G, eIF4A, eIF4B, cap-binding complex, translation initiation, protein abundance, translational regulation, cell size control, Saccharomyces cerevisiae, protein synthesis
- MeSH terms
- Animals, Phosphoproteins, Rabbits, RNA Caps, RNA, Viral, Saccharomyces cerevisiae, Protein Biosynthesis, Gene Expression Regulation, Fungal, Saccharomyces cerevisiae Proteins, Nuclear Cap-Binding Protein Complex, Eukaryotic Initiation Factor-4E, Eukaryotic Initiation Factors
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