Two zebrafish eIF4E family members are differentially expressed and functionally divergent.

Javier Robalino,Bhavesh Joshi,Rosemary Jagus,Scott C. Fahrenkrug

doi:10.1074/jbc.m313688200

Javier Robalino, Bhavesh Joshi + Show 2 more

Open Access

https://doi.org/10.1074/jbc.m313688200

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Abstract

Eukaryotic translation initiation factor 4E (eIF4E) is an essential component of the translational machinery that binds m(7)GTP and mediates the recruitment of capped mRNAs by the small ribosomal subunit. Recently, a number of proteins with homology to eIF4E have been reported in plants, invertebrates, and mammals. Together with the prototypical translation factor, these constitute a new family of structurally related proteins. To distinguish the prototypical translation factor eIF4E from other family members, it has been termed eIF4E-1 (Keiper, B. D., Lamphear, B. J., Deshpande, A. M., Jankowska-Anyszka, M., Aamodt, E. J., Blumenthal, T., and Rhoads, R. E. (2000) J. Biol. Chem. 275, 10590-10596). We describe the characterization of two eIF4E family members in the zebrafish Danio rerio. Based on their relative identities with human eIF4E-1, these zebrafish proteins are termed eIF4E-1A (82%) and eIF4E-1B (66%). eIF4E-1B, originally termed eIF4E(L), has been reported previously as the zebrafish eIF4E-1 counterpart (Fahrenkrug, S. C., Dahlquist, M. O., Clark, K., and Hackett, P. B. (1999) Differentiation 65, 191-201; Fahrenkrug, S. C., Joshi, B., Hackett, P. B., and Jagus, R. (2000) Differentiation 66, 15-22). Sequence comparisons suggest that the two genes probably evolved from a duplication event that occurred during vertebrate evolution. eIF4E-1A is expressed ubiquitously in zebrafish, whereas expression of eIF4E-1B is restricted to early embryonic development and to gonads and muscle of the tissues investigated. The ability of these two zebrafish proteins to bind m(7)GTP, eIF4G, and 4E-BP, as well as to complement yeast conditionally deficient in functional eIF4E, show that eIF4E-1A is a functional equivalent of human eIF4E-1. Surprisingly, although eIF4E-1B possesses all known residues thought to be required for interaction with the cap structure, eIF4G, and 4E-BPs, it fails to interact with any of these components, suggesting that this protein serves a role other than that assigned to eIF4E.

Highlights

¶ Supported by scholarships from Fundacion para la Ciencia y Tecnologıa, Ecuador
Our studies have shown that zebrafish eukaryotic initiation factor 4E (eIF4E)-1A appears to represent the functional equivalent of human eIF4E-1
The translation factor, eIF4E, functions to recruit mRNA to the ribosome by binding simultaneously to the 5Ј cap structure and to the scaffold translation factor eIF4G

Summary

Introduction

¶ Supported by scholarships from Fundacion para la Ciencia y Tecnologıa, Ecuador. Present address: Medical University of South Carolina, 173 Ashley Ave., Charleston, SC 29425. The ability of these two zebrafish proteins to bind m7GTP, eIF4G, and 4E-BP, as well as to complement yeast conditionally deficient in functional eIF4E, show that eIF4E-1A is a functional equivalent of human eIF4E-1.

Results

Conclusion