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.

Advances in the study of RNA-binding proteins in diabetic complications

“…Eukaryotic initiation factor 4E (EIF-4E) is an mRNA cap-binding protein that is considered to be a universal promoter affecting mRNA-ribosome interactions and capture-dependent translation in eukaryotic cells [ 108 ]. By interacting with eukaryotic initiation factor 4G (EIF-4G), it specifically associates with the 7-methylguanosine cap located at the 5′ end of eukaryotic mRNA, thereby promoting the migration of mRNA to the ribosome and playing a core role in translation initiation [ 99 ].…”

“…Mammalian rapamycin complex 1 (mTORC1) is one of the key regulators of growth and metabolism in cells, and downstream effectors of its regulation include EIF-4EBPs and ribosomal protein S6K kinase (RP-S6K) [ 110 ]. Current research on EIF-4E focused on its role in cancer cell growth regulation and growth factors amplification [ 108 ]. Many works also support an important role of EIF-4E in diabetic macroangiopathy as well.…”

The In Silico Identification of Potential Members of the Ded1/DDX3 Subfamily of DEAD-Box RNA Helicases from the Protozoan Parasite Leishmania infantum and Their Analyses in Yeast

“…Interestingly, LINF_070008800 showed multiple repeats of potential eIF4E binding motifs. However, it should be noted that trypanosomatids have at least six variant eIF4E proteins that are structurally different from those of other organisms due to the unusual cap-4 structure on their mRNAs (reviewed by [ 49 , 91 , 92 ]). Indeed, none of the tested Leishmania eIF4E proteins complement a yeast strain deleted for the essential eIF4E gene [ 93 ].…”

Functional Micropeptides Encoded by Long Non-Coding RNAs: A Comprehensive Review

“…The micropeptide STORM encoded by linc00689 is regulated by phosphorylation of the eukaryotic translation initiation factor 4E (eIF4E) which is mediated by TNF-α and mammalian Ste20-like kinase (MST1) ( Min et al, 2017 ). eIF4E is an mRNA cap-binding protein that is a general initiation factor allowing for mRNA-ribosome interaction and cap-dependent translation in eukaryotic cells ( Ross-Kaschitza and Altmann, 2020 ). Phosphorylation of eIF4E was found to weaken the interaction with 5' cap while inhibiting mRNA translation, but enhanced the association of active polyribosomes with lncRNA ( Min et al, 2017 ).…”