The alveolate translation initiation factor 4E family reveals a custom toolkit for translational control in core dinoflagellates

Abstract

BackgroundDinoflagellates are eukaryotes with unusual cell biology and appear to rely on translational rather than transcriptional control of gene expression. The eukaryotic translation initiation factor 4E (eIF4E) plays an important role in regulating gene expression because eIF4E binding to the mRNA cap is a control point for translation. eIF4E is part of an extended, eukaryote-specific family with different members having specific functions, based on studies of model organisms. Dinoflagellate eIF4E diversity could provide a mechanism for dinoflagellates to regulate gene expression in a post-transcriptional manner. Accordingly, eIF4E family members from eleven core dinoflagellate transcriptomes were surveyed to determine the diversity and phylogeny of the eIF4E family in dinoflagellates and related lineages including apicomplexans, ciliates and heterokonts.ResultsThe survey uncovered eight to fifteen (on average eleven) different eIF4E family members in each core dinoflagellate species. The eIF4E family members from heterokonts and dinoflagellates segregated into three clades, suggesting at least three eIF4E cognates were present in their common ancestor. However, these three clades are distinct from the three previously described eIF4E classes, reflecting diverse approaches to a central eukaryotic function. Heterokonts contain four clades, ciliates two and apicomplexans only a single recognizable eIF4E clade. In the core dinoflagellates, the three clades were further divided into nine sub-clades based on the phylogenetic analysis and species representation. Six of the sub-clades included at least one member from all eleven core dinoflagellate species, suggesting duplication in their shared ancestor. Conservation within sub-clades varied, suggesting different selection pressures.ConclusionsPhylogenetic analysis of eIF4E in core dinoflagellates revealed complex layering of duplication and conservation when compared to other eukaryotes. Our results suggest that the diverse eIF4E family in core dinoflagellates may provide a toolkit to enable selective translation as a strategy for controlling gene expression in these enigmatic eukaryotes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-015-0301-9) contains supplementary material, which is available to authorized users.

Biosynthesis of Saxitoxin in Marine Dinoflagellates: An Omics Perspective

“…Abundance and activities of protein elF4E often become the target for translational control, as seen in the phosphorylation of protein elF4E that regulates the circadian protein expression [82]. Recent discovery of an extensive transcript encoding the protein elF4E family in dinoflagellates provides additional evidence for substantial translational control in dinoflagellates [83].…”

“…Enzyme in the TCA cycle exhibited circadian changes in accordance with protein abundance, whereas its messenger RNA (mRNA) level remained constant throughout the cycle [84] Presence of unique splice leader at 5' of dinoflagellates mRNA might provide translational regulation in dinoflagellates via trans-splicing [72,73] Expression of conserved S-phase genes in Karenia brevis remains unchanged throughout cell cycle, but other protein expression level was observed [85] Presence of dinoflagellate spliced leader sequence at 5' of sxtA and sxtG genes might indicate that saxitoxin biosynthesis is regulated at the translational level [43,44] Daily circadian system in dinoflagellate Lingulodinium showed lack of regulation at the transcript level using RNA-sequencing approach, suggesting the involvement of translational or post-translational control of this system [86] Identification of microRNAs (miRNAs) in several species of dinoflagellates, including saxitoxin-producing dinoflagellates, indicates regulation of several genes in dinoflagellates at post-transcriptional level via a small RNA gene silencing mechanism [76][77][78][79][80] Characterization of extensive transcript encoding protein elF4E family in dinoflagellates [83] Genome sequence of Symbiodinium kawagutii revealed substantial translational control by miRNA in biological processes involving carbohydrate metabolism, transcription regulation, and biosynthesis of amino acids and antibiotics [79] Poor correlation between protein and mRNA level in dinoflagellate Lingulodinium [87]…”

eIF4E and Interactors from Unicellular Eukaryotes

“…Dinoflagellate species vary enormously considering the size of their genome which ranges from a few to a hundred thousand Mbytes and they have particular nuclear features (e.g., permanently condensed chromosomes) that make them very different from other eukaryotes. Similar to protozoan parasites, their mRNAs are also trans-spliced from polycistronic primary transcripts to form cap4-like monocistronic mRNAs and several options have been identified as alternative for the nucleotide that follows the first trimethylated base [21]. As for protozoan parasites described in this review (Trypanosomatidae), regulation of gene expression is posttranscriptional [102].…”

“…eIF4E8 or 4E-HP has been shown to act as a mRNA-specific inhibitor of eIF4E-activity during embryogenesis [15,18,19]. Variations in the arrangement of the conserved tryptophane residues has allowed for classification of metazoan eIF4Es as class 1, 2 or 3 [17,21]. While class 1 carries all eight tryptophanes, class 2 members possess W1 modified to Y, F, or L and W3 to Y or F. Rare class 3 carry W1 but W3 is replaced by C or Y.…”

Diverse cap-binding properties of Drosophila eIF4E isoforms

“…On the other side, they have shown that cap nucleotides interact with a narrow slot on the concave surface of eIF4E. The interatomic contacts between eIF4E proteins and cap analogues can be divided into three classes: (i) sandwiching of the 7-methyl guanine between two tryptophan residues (in Class I eIF4E isoforms) or a tryptophan and a tyrosine residues (in Class II); (ii) hydrogen bonds and van der Walls contacts with the 7-methylguanosine; and (iii) direct interactions and water-mediated contacts with the phosphate chains of a cap structure and a positively charged pocket of the cap-binding slot of eIF4E formed by the side chains of several Lys and Arg residues [12,33,35].…”