eIF4E orchestrates mRNA processing, RNA export and translation to modify specific protein production

Jean Clément Mars, Biljana Culjkovic-Kraljacic, Katherine L.B. Borden*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

The eukaryotic translation initiation factor eIF4E acts as a multifunctional factor that simultaneously influences mRNA processing, export, and translation in many organisms. Its multifactorial effects are derived from its capacity to bind to the methyl-7-guanosine cap on the 5’end of mRNAs and thus can act as a cap chaperone for transcripts in the nucleus and cytoplasm. In this review, we describe the multifactorial roles of eIF4E in major mRNA-processing events including capping, splicing, cleavage and polyadenylation, nuclear export and translation. We discuss the evidence that eIF4E acts at two levels to generate widescale changes to processing, export and ultimately the protein produced. First, eIF4E alters the production of components of the mRNA processing machinery, supporting a widescale reprogramming of multiple mRNA processing events. In this way, eIF4E can modulate mRNA processing without physically interacting with target transcripts. Second, eIF4E also physically interacts with both capped mRNAs and components of the RNA processing or translation machineries. Further, specific mRNAs are sensitive to eIF4E only in particular mRNA processing events. This selectivity is governed by the presence of cis-acting elements within mRNAs known as USER codes that recruit relevant co-factors engaging the appropriate machinery. In all, we describe the molecular bases for eIF4E’s multifactorial function and relevant regulatory pathways, discuss the basis for selectivity, present a compendium of ~80 eIF4E-interacting factors which play roles in these activities and provide an overview of the relevance of its functions to its oncogenic potential. Finally, we summarize early-stage clinical studies targeting eIF4E in cancer.

Original languageEnglish (US)
Article number2360196
JournalNucleus
Volume15
Issue number1
DOIs
StatePublished - 2024

Funding

This work was supported by NIH R01 CA80728, NIH R01 CA98571, Canadian Institutes of Health Research PJT159785, and the Canada Research Chair in Molecular Biology of the Cell Nucleus. We thank Michael Osborne for reading and helpful comments and for assistance generating Figure 2.

Keywords

  • Cap binding protein
  • capping
  • eIF4E
  • gene expression
  • m7G cap
  • mRNA export
  • mRNA maturation
  • mRNA processing
  • splicing
  • translation

ASJC Scopus subject areas

  • Cell Biology

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