Mextli Is a Novel Eukaryotic Translation Initiation Factor 4E-Binding Protein That Promotes Translation in Drosophila melanogaster

Abstract

Translation is a fundamental step in gene expression, and translational control is exerted in many developmental processes. Most eukaryotic mRNAs are translated by a cap-dependent mechanism, which requires recognition of the 5′-cap structure of the mRNA by eukaryotic translation initiation factor 4E (eIF4E). eIF4E activity is controlled by eIF4E-binding proteins (4E-BPs), which by competing with eIF4G for eIF4E binding act as translational repressors. Here, we report the discovery of Mextli (Mxt), a novel Drosophila melanogaster 4E-BP that in sharp contrast to other 4E-BPs, has a modular structure, binds RNA, eIF3, and several eIF4Es, and promotes translation. Mxt is expressed at high levels in ovarian germ line stem cells (GSCs) and early-stage cystocytes, as is eIF4E-1, and we demonstrate the two proteins interact in these cells. Phenotypic analysis of mxt mutants indicates a role for Mxt in germ line stem cell (GSC) maintenance and in early embryogenesis. Our results support the idea that Mxt, like eIF4G, coordinates the assembly of translation initiation complexes, rendering Mxt the first example of evolutionary convergence of eIF4G function.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.01354-12.

ACKNOWLEDGMENTS

We are thankful to Paula Vázquez-Pianzola for plasmids and protocols, Gritta Tettweiler for protocols, Stanley Fields and the Drosophila Genomics Resource Center (DGRC) for plasmids, José Manuel Sierra, Matthias Hentze, Sandra Wolin, and Isabel Palacios for antibodies, Armen Parsyan, Bruno Fonseca, and Thomas Sundermeier for useful discussions, and Beili Hu for microinjections.

This work was supported by grant MOP-44050 to P.L. and N.S. from the Canadian Institutes of Health Research.