Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms
Open accessAbstract
Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5′-end of the mRNA to promote the recruitment of the ribosome. Although the 3′ poly(A) tail of eukaryotic mRNAs and its major bound protein, the poly(A)-binding protein (PABP), have been studied extensively, their mechanism of action in translation is not well understood and is confounded by differences between in vivo and in vitro systems. Here, we provide direct evidence for the involvement of PABP in key steps of the translation initiation pathway. Using a new technique to deplete PABP from mammalian cell extracts, we show that extracts lacking PABP exhibit dramatically reduced rates of translation, reduced efficiency of 48S and 80S ribosome initiation complex formation, and impaired interaction of eIF4E with the mRNA cap structure. Supplementing PABP-depleted extracts with wild-type PABP completely rectified these deficiencies, whereas a mutant of PABP, M161A, which is incapable of interacting with eIF4G, failed to restore translation. In addition, a stronger inhibition (approximately twofold) of 80S as compared to 48S ribosome complex formation (∼65% vs. ∼35%, respectively) by PABP depletion suggests that PABP plays a direct role in 60S subunit joining. PABP can thus be considered a canonical translation initiation factor, integral to initiation complex formation at the 5′-end of mRNA.
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The polyA tail stabilizes and improves translation initiation efficiency in linear mRNA through the actions of polyadenylate binding proteins.
“Similarly, the polyA tail stabilizes and improves translation initiation efficiency in linear mRNA through the actions of polyadenylate binding proteins24, 25.”
From Engineering circular RNA for potent and stable translation in eukaryotic cells (2018) · cites this paper as [25]
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Cites
eIF4 Initiation Factors: Effectors of mRNA Recruitment to Ribosomes and Regulators of Translation
Gingras, A., Raught, B., & Sonenberg, N. (1999) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.68.1.913 · Cited by 2,103 · see citing works
Self-citationThe cap and poly(A) tail function synergistically to regulate mRNA translational efficiency.
Gallie, D. R. (1991) · Genes & Development · doi:10.1101/gad.5.11.2108 · Cited by 868 · 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
Mangus, D. A., Evans, M. C., & Jacobson, A. (2003) · Genome biology · doi:10.1186/gb-2003-4-7-223 · Cited by 601 · see citing works
Imataka, H., Gradi, A., & Sonenberg, N. (1998) · The EMBO Journal · doi:10.1093/emboj/17.24.7480 · Cited by 572 · see citing works
Self-citationSachs, A. B., & Davis, R. W. (1989) · Cell · doi:10.1016/0092-8674(89)90938-0 · Cited by 571 · see citing works
Ostareck, D. H., Ostareck‐Lederer, A., Wilm, M. S., Thiele, B. J., Mann, M., & Hentze, M. W. (1997) · Cell · doi:10.1016/s0092-8674(00)80241-x · Cited by 503 · see citing works
Svitkin, Y. V., Pause, A., Haghighat, A., Pyronnet, S., Witherell, G. W., Belsham, G. J., & Sonenberg, N. (2001) · RNA · doi:10.1017/s135583820100108x · Cited by 477 · see citing works
Self-citationPause, 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
Self-citationA common function for mRNA 5' and 3' ends in translation initiation in yeast.Preprint
Tarun, S. Z., & Sachs, A. B. (1995) · Genes & Development · doi:10.1101/gad.9.23.2997 · Cited by 374 · see citing works
Ribosome loading onto the mRNA cap is driven by conformational coupling between eIF4G and eIF4E.
Gross, J., Moerke, N., von der Haar, T., Lugovskoy, A., Sachs, A., McCarthy, J., & Wagner, G. (2003) · Cell · doi:10.1016/s0092-8674(03)00975-9 · Cited by 368 · see citing works
Sonenberg, N., Morgan, M. A., Merrick, W. C., & Shatkin, A. J. (1978) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.75.10.4843 · Cited by 367 · see citing works
Self-citationmRNA poly(A) tail, a 3' enhancer of translational initiation.
Munroe, D. J., & Jacobson, A. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.7.3441 · Cited by 351 · see citing works
Piron, M., Vende, P., Cohen, J., et al. (1998) · The EMBO Journal · doi:10.1093/emboj/17.19.5811 · Cited by 334 · see citing works
A Mechanism for Translationally Coupled mRNA Turnover
Grosset, C., Chen, C.-Y. A., Xu, N., Sonenberg, N., Jacquemin-Sablon, H., & Shyu, A.-B. (2000) · Cell · doi:10.1016/s0092-8674(00)00102-1 · Cited by 295 · see citing works
Self-citationGallie, D. R. (1998) · Gene · doi:10.1016/s0378-1119(98)00318-7 · Cited by 280 · see citing works
Ostareck, D., Ostareck-Lederer, A., Shatsky, I., & Hentze, M. (2001) · Cell · doi:10.1016/s0092-8674(01)00212-4 · Cited by 280 · see citing works
Gray, N. K., & Hentze, M. W. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06699.x · Cited by 276 · see citing works
Iizuka, N., Najita, L., Franzusoff, A., & Sarnow, P. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.11.7322 · Cited by 275 · see citing works
Le, H., Tanguay, R. L., Balasta, M. L., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.26.16247 · Cited by 262 · see citing works
eIF4G Dramatically Enhances the Binding of eIF4E to the mRNA 5′-Cap Structure
Haghighat, A., & Sonenberg, N. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.35.21677 · Cited by 239 · see citing works
Self-citationMultiple portions of poly(A)‐binding protein stimulate translation in vivo
Gray, N. K., Coller, J. M., Dickson, K. S., & Wickens, M. (2000) · The EMBO Journal · doi:10.1093/emboj/19.17.4723 · Cited by 236 · see citing works
Involvement of eukaryotic initiation factor 4A in the cap recognition process.
Edery, I., Hümbelin, M., Darveau, A., Lee, K. A. W., Milburn, S. C., Hershey, J. W. B., Trachsel, H., & Sonenberg, N. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)44431-0 · Cited by 221 · see citing works
Self-citationA Conserved HEAT Domain within eIF4G Directs Assembly of the Translation Initiation Machinery
Marcotrigiano, J., Lomakin, I. B., Sonenberg, N., Pestova, T. V., Hellen, C. U. T., & Burley, S. K. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00167-8 · Cited by 216 · see citing works
Self-citationTranslational Repression by a Novel Partner of Human Poly(A) Binding Protein, Paip2
Khaleghpour, K., Svitkin, Y. V., Craig, A. W., DeMaria, C. T., Deo, R. C., Burley, S. K., & Sonenberg, N. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00168-x · Cited by 212 · see citing works
Self-citationThe mRNA Closed-loop Model: The Function of PABP and PABP-interacting Proteins in mRNA TranslationPreprint
Kahvejian, A., Roy, G., & Sonenberg, N. (2001) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2001.66.293 · Cited by 183 · see citing works
Self-citationCap-Poly(A) Synergy in Mammalian Cell-free Extracts
Michel, Y. M., Poncet, D., Pirón, M., Kean, K. M., & Borman, A. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004304200 · Cited by 159 · see citing works
Dual Interactions of the Translational Repressor Paip2 with Poly(A) Binding Protein
Khaleghpour, K., Kahvejian, A., Crescenzo, G. D., Roy, G., Svitkin, Y. V., Imataka, H., O'Connor‐McCourt, M. D., & Sonenberg, N. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.15.5200-5213.2001 · Cited by 159 · see citing works
Self-citationATP/Mg++-dependent cross-linking of cap binding proteins to the 5′ end of eukaryotic mRNA
Sonenberg, N. (1981) · Nucleic Acids Research · doi:10.1093/nar/9.7.1643 · Cited by 150 · see citing works
Self-citationStabilization 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
Poly(A)-binding protein interaction with elF4G stimulates picornavirus IRES-dependent translation.
Svitkin, Y. V., Imataka, H., Khaleghpour, K., Kahvejian, A., Liebig, H., & Sonenberg, N. (2001) · Europe PMC (PubMed Central) · Cited by 138 · see citing works
Self-citationmRNA Poly (A) Tail, a 3′ Enhancer of Translational Initiation
Munroe, D. J., & Jacobson, A. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.7.3441-3455.1990 · Cited by 138 · see citing works
Recognition of eIF4G by Rotavirus NSP3 Reveals a Basis for mRNA Circularization
Groft, C. M., & Burley, S. K. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00555-5 · Cited by 133 · see citing works
Wei, C., Balasta, M. L., Ren, J., & Goss, D. J. (1998) · Biochemistry · doi:10.1021/bi9724570 · Cited by 132 · see citing works
Otero, L. J., Ashe, M. P., & Sachs, A. B. (1999) · The EMBO Journal · doi:10.1093/emboj/18.11.3153 · Cited by 127 · see citing works
Wakiyama, M., Imataka, H., & Sonenberg, N. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00701-6 · Cited by 126 · see citing works
Self-citationLodish, H. F., & Rose, J. K. (1977) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)40638-7 · Cited by 122 · see citing works
2 The Pathway and Mechanism of Initiation of Protein SynthesisPreprint
Hershey, J. W. B., & Merrick, W. C. (2000) · Cold Spring Harbor Monograph Archive · doi:10.1101/087969618.39.33 · Cited by 115 · see citing works
The mechanism and regulation of deadenylation: Identification and characterization of Xenopus PARN
Copeland, P. R., & Wormington, M. (2001) · RNA · doi:10.1017/s1355838201010020 · Cited by 112 · see citing works
Lee, K. A., & Sonenberg, N. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.11.3447 · Cited by 107 · see citing works
Self-citationSearfoss, A. M., Dever, T., & Wickner, R. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.15.4900-4908.2001 · Cited by 105 · see citing works
Iizuka, N., Najita, L., Franzusoff, A., et al. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.11.7322-7330.1994 · Cited by 103 · see citing works
Pelletier, J., & Sonenberg, N. (1985) · Molecular and Cellular Biology · doi:10.1128/mcb.5.11.3222-3230.1985 · Cited by 102 · see citing works
Self-citationPoncet, D., Aponte, C., & Cohen, J. (1993) · Journal of Virology · doi:10.1128/jvi.67.6.3159-3165.1993 · Cited by 98 · see citing works
Byrd, M. P., Zamora, M., & Lloyd, R. E. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.13.4499-4511.2002 · Cited by 87 · see citing works
An Efficient System for Cap- and Poly(A)-Dependent Translation In Vitro
Svitkin, Y. V., & Sonenberg, N. (2004) · Humana Press eBooks · doi:10.1385/1-59259-750-5:155 · Cited by 80 · see citing works
Self-citationBi, X., & Goss, D. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m909464199 · Cited by 73 · see citing works
Afonina, E., Neumann, M., & Pavlakis, G. N. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.4.2307 · Cited by 66 · see citing works
Svitkin, Y. V., & Agol, V. I. (1978) · FEBS Letters · doi:10.1016/0014-5793(78)80121-5 · Cited by 51 · see citing works
Self-citation16 Poly(A) Metabolism and Translation: The Closed-loop ModelPreprint
Jacobson, A. (1996) · Cold Spring Harbor Monograph Archive · doi:10.1101/087969458.30.451 · Cited by 33 · see citing works
Assays for Eukaryotic Translation Factors That Bind mRNA
Merrick, W. C., & Sonenberg, N. (1997) · Methods · doi:10.1006/meth.1996.0431 · Cited by 14 · see citing works
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Research works printed but not linked: 1
- Sachs, A. 2000. Physical and functional interactions between the mRNA cap structure and the poly(A) tail. in Transla- tional control of gene expression (ed. M.B. Mathews), pp. 447-466. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
Cited by
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Regulation of mRNA Translation and Stability by microRNAs
Fabian, M. R., Sonenberg, N., & Filipowicz, W. (2010) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060308-103103 · Cited by 3,214 · see citing works
Self-citationRegulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets
Sonenberg, N., & Hinnebusch, A. G. (2009) · Cell · doi:10.1016/j.cell.2009.01.042 · Cited by 3,304 · see citing works
“PABP also stimulates 60S subunit joining (Kahvejian et al., 2005), and findings from yeast suggest that the poly(A) tail is required to block the inhibitory effects of two RNA helicases on subunit joining factor eIF5B (Searfoss et al.”
Self-citationEngineering circular RNA for potent and stable translation in eukaryotic cells
Wesselhoeft, R. A., Kowalski, P. S., & Anderson, D. G. (2018) · Nature Communications · doi:10.1038/s41467-018-05096-6 · Cited by 884 · see citing works
Targeting the eIF4F Translation Initiation Complex: A Critical Nexus for Cancer Development
Pelletier, J., Graff, J., Ruggero, D., & Sonenberg, N. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-2789 · Cited by 367 · see citing works
Self-citationTranslational control by changes in poly(A) tail length: recycling mRNAs
Weill, L., Belloc, E., Bava, F.-A., & Méndez, R. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2311 · Cited by 328 · see citing works
Kwon, H., Kim, M., Seo, Y., Moon, Y. S., Lee, H. J., Lee, K., & Lee, H. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2017.11.034 · Cited by 208 · see citing works
Patton, R. D., Sanjeev, M., Woodward, L. A., Mabin, J. W., Bundschuh, R., & Singh, G. (2020) · RNA · doi:10.1261/rna.074856.120 · Cited by 46 · see citing works
Fehler, O., Singh, P., Haas, A., Ulrich, D., Müller, J. P., Ohnheiser, J., & Klempnauer, K.-H. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku800 · Cited by 35 · see citing works
- Authors
- Kahvejian, A., Svitkin, Y. V., Sukarieh, R., M'Boutchou, M.-N., & Sonenberg, N.
- Affiliations
- McGill University (CA)
- Corresponding author
- Sonenberg, Nahum
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-01-01
- Volume
- 19
- Issue
- 1
- Pages
- 104-113
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC540229
- OpenAlex
- W2129069292
- Cited by
- 491
- References
- 51
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 19 · 2023: 13 · 2022: 11 · 2021: 33 · 2020: 18 · 2019: 22 · 2018: 21 · 2017: 23 · 2016: 26 · 2015: 16 · 2014: 31 · 2013: 21 · 2012: 22
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@McGill (McGill) (submittedVersion, cc-by-nc)
- Funders
- McGill University
- Faculty of Medicine, McGill University
- National Institutes of Health
- Canadian Institutes of Health Research
- National Institute of General Medical Sciences (5R01 GM66157-03, R01GM066157)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- poly(A)-binding protein, translation initiation, eIF4G, eIF4E, mRNA cap, 48S initiation complex, 80S ribosome assembly, poly(A) tail
- MeSH terms
- Animals, Cell Extracts, Humans, Protein Binding, Ribosomes, Protein Biosynthesis, Poly(A)-Binding Protein I, Eukaryotic Initiation Factor-4G, Eukaryotic Initiation Factors
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