eIF4E and Interactors from Unicellular Eukaryotes

Abstract

eIF4E, the mRNA cap-binding protein, is well known as a general initiation factor allowing for mRNA-ribosome interaction and cap-dependent translation in eukaryotic cells. In this review we focus on eIF4E and its interactors in unicellular organisms such as yeasts and protozoan eukaryotes. In a first part, we describe eIF4Es from yeast species such as Saccharomyces cerevisiae, Candida albicans, and Schizosaccharomyces pombe. In the second part, we will address eIF4E and interactors from parasite unicellular species-trypanosomatids and marine microorganisms-dinoflagellates. We propose that different strategies have evolved during evolution to accommodate cap-dependent translation to differing requirements. These evolutive "adjustments" involve various forms of eIF4E that are not encountered in all microorganismic species. In yeasts, eIF4E interactors, particularly p20 and Eap1 are found exclusively in Saccharomycotina species such as S. cerevisiae and C. albicans. For protozoan parasites of the Trypanosomatidae family beside a unique cap4-structure located at the 5'UTR of all mRNAs, different eIF4Es and eIF4Gs are active depending on the life cycle stage of the parasite. Additionally, an eIF4E-interacting protein has been identified in Leishmania major which is important for switching from promastigote to amastigote stages. For dinoflagellates, little is known about the structure and function of the multiple and diverse eIF4Es that have been identified thanks to widespread sequencing in recent years.

Keywords: eIF4E; eIF4E-interactors; protozoan parasites; translation; yeast.

Figure 1

3D structure (1RF8) of S. cerevisiae eIF4E (gold) in complex with eIF4G (grey; aa 393 to 490). Displayed in red are aromatic residues W3, W5 and W8 in the cap-binding groove and aromatic residue W4 located at the dorsal part of eIF4E which interacts with eIF4G. Highlighted in yellow is the conserved S/TVxxF motif forming helix1 next to W4. Phosphorylated residue S28 of S. cerevisiae eIF4E is displayed in blue.

Figure 2

(A) Scheme representing the core of different yeast eIF4E1 and eIF4E2 including the eight conserved tryptophane residues W1 to W8 (labelled in red), substitutions of W3 for Y (labelled in grey). Highlighted in orange is the conserved aminoterminus (motif MSENLKRAESLFNRIMN) found in several eIF4E2s of Saccharomycotina species, marked in yellow is the helix-forming motif S/TVxxF adjacent to W4 of all shown yeast eIF4E1 and S. pombe eIF4E2 (but not conserved in Saccharomycotina eIF4E2s). (B) Phylogenetic summary of eIF4E1, eIF4E2, Eap1, and p20 from yeast species of different subphyla and families. (i) Eap1 containing species are marked in blue; (ii) p20 containing species in dark green for families Metschnikowiaceae or Debaryomycetaceae and light green for families Pichiaceae, Phaffomycetaceae, Saccharomycodaceae, Saccharomycetaceae, and Ascoideaceae. (iii) eIF4E1 (yellow) is present in all species; (iv) eIF4E2 containing species from Taphrinomycotina (dark orange), from families Metschnikowiaceae or Debaryomycetaceae (light orange) and from Pichiaceae (salmon).

Figure 3

(A) Scheme representing eIF4G and other eIF4E-interacting proteins from different species (as indicated in the cartoon). All proteins are aligned according to their canonical (in green) and non-canonical (violet) eIF4E-binding sites that were shown directly by solving 3D structures of eIF4E in complex with the 4E-BPs (5T46, 6FC1, 4UED, 6FC3, 6FC2). HEAT/MIF-4G domains are displayed in dark grey. (B) Sequences of the canonical (green) and non-canonical eIF4E-binding (violet) amino acid motifs from different species aligned according to the canonical eIF4E-binding motif YxxxLΦ (bold).

Figure 3

(A) Scheme representing eIF4G and other eIF4E-interacting proteins from different species (as indicated in the cartoon). All proteins are aligned according to their canonical (in green) and non-canonical (violet) eIF4E-binding sites that were shown directly by solving 3D structures of eIF4E in complex with the 4E-BPs (5T46, 6FC1, 4UED, 6FC3, 6FC2). HEAT/MIF-4G domains are displayed in dark grey. (B) Sequences of the canonical (green) and non-canonical eIF4E-binding (violet) amino acid motifs from different species aligned according to the canonical eIF4E-binding motif YxxxLΦ (bold).

Figure 4

(A) Chemical representation of cap4-structure from Trypanosomatids (taken from Zinoviev and Shapira [81]). (B) Scheme representing the core of Leishmania major eIF4E1 to eIF4E6 (accession numbers in brackets) including the eight conserved tryptophane residues W1 to W8 (highlighted in red), substitutions of W2, W3, W4, W5, W6, or W7 for Y, F, or L are labelled in grey. Highlighted in yellow is the conserved helix-forming motif S/TVxxF next to W4 of Leishmania eIF4E1.

Figure 5

Scheme representing the core of dinoflagellate eIF4E1a, eIF4E2a, and eIF4E3a from Amphidinium carterae (accession numbers in brackets) including the eight conserved tryptophane residues W1 to W8 (labelled in red), and substitutions of W3, W4, and W6 for Y or F (labelled in grey). Highlighted in yellow is also the conserved helix-forming motif STVxxF next to W4.