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Review

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

ORCID Icon, ORCID Icon & ORCID Icon
Article: 2360196 | Received 12 Feb 2024, Accepted 22 May 2024, Published online: 16 Jun 2024

Figures & data

Table 1. Summary of eIF4E partner proteins.

Figure 1. A, Single section of confocal imaging of U2OS cells stained for eIF4E (sc-271480 anti-eIF4E antibody, red) and DAPI (blue, nuclear dye) showing nuclear and cytoplasmic localization. Left panel shows the overlap between DAPI and eIF4E staining. The right panel shows eIF4E signal alone. B, Confocal imaging of eIF4E in the nucleus of HeLa cells with the antibody 10C6 from [Citation101]. Reprint with permission from Dostie J, Lejbkowicz F, Sonenberg N. Nuclear eukaryotic initiation factor 4E (eIF4E) colocalizes with splicing factors in speckles [Citation99]. White bar = 10μm.

A. The top left panel shows DAPI staining of nuclei of three individual U2OS cells merged with the red signal of eIF4E staining, and on the right panel, the staining for eIF4E alone is seen in the same cells. Enrichment of eIF4E in the nuclei of cells is clear, cytoplasmic signal is also visible, showing a particulate and dispersed pattern through the nucleus and cytoplasm. B. The bottom left panel represents the phase contrast image of the two HeLa cells. The right panel represents eIF4E staining of the same cells showing predominantly nuclear localization.
Figure 1. A, Single section of confocal imaging of U2OS cells stained for eIF4E (sc-271480 anti-eIF4E antibody, red) and DAPI (blue, nuclear dye) showing nuclear and cytoplasmic localization. Left panel shows the overlap between DAPI and eIF4E staining. The right panel shows eIF4E signal alone. B, Confocal imaging of eIF4E in the nucleus of HeLa cells with the antibody 10C6 from [Citation101]. Reprint with permission from Dostie J, Lejbkowicz F, Sonenberg N. Nuclear eukaryotic initiation factor 4E (eIF4E) colocalizes with splicing factors in speckles [Citation99]. White bar = 10μm.

Figure 3. eIF4E can directly influence RNA fate or indirectly through its capacity to terraform the RNA processing landscape. On the left, interactions between eIF4E target mRNAs and the noted machineries are shown. On the right, numbers of mRNAs in a given process were identified in nuclear, endogenous eIF4E RIP-Seq [Citation54] GSE63265_LY1_4EIP_allreps_counts.Txt.gz and/or RNA-seq splicing data segregated on high and normal-eIF4E AML specimens [Citation100] (https://leucegene.ca/). These strongly suggest that eIF4E can influence a broad array of factors responsible for RNA processing thereby terraforming the RNA processing landscape. Functional categories were assigned using Metascape (metascape.Org).

On the left, the major mRNA nuclear maturation steps are shown noting the involvement of eIF4E, as well as specific interacting partners discussed in the text. See the text for more details. On the right, the numbers of mRNAs coding for proteins involved in different mRNA processing steps that are targeted by eIF4E observed in nuclear, endogenous eIF4E-RIP-Seq and/or differentially spliced in AML patients based on eIF4E levels.
Figure 3. eIF4E can directly influence RNA fate or indirectly through its capacity to terraform the RNA processing landscape. On the left, interactions between eIF4E target mRNAs and the noted machineries are shown. On the right, numbers of mRNAs in a given process were identified in nuclear, endogenous eIF4E RIP-Seq [Citation54] GSE63265_LY1_4EIP_allreps_counts.Txt.gz and/or RNA-seq splicing data segregated on high and normal-eIF4E AML specimens [Citation100] (https://leucegene.ca/). These strongly suggest that eIF4E can influence a broad array of factors responsible for RNA processing thereby terraforming the RNA processing landscape. Functional categories were assigned using Metascape (metascape.Org).

Table 2. Summary of RNA processing factors that are regulated by eIF4E.

Figure 2. The human eIF4E structure binding the m7G cap (in red) and known interactions: eIF4E structure and relative position of regions utilized by known partner proteins. The red arrow indicates the cap-binding site with the associated tryptophans in light blue, the purple arrow indicates the positively charge patch, where Importin 8, VPg and EG5 bind with the 2 lysines and the arginine shown. The dorsal surface is also shown and as is the surface used by the NC (non- canonical domain) of eIF4G and 4EBPs with gold yellow arrows (Adapted from [Citation52], PDB3AM7).

Structure of human eIF4E proteins binding the m7G cap with indication of the cap-binding site, the positively charged patch, and the dorsal surface. Selected interacting proteins are indicated for each of these domains.
Figure 2. The human eIF4E structure binding the m7G cap (in red) and known interactions: eIF4E structure and relative position of regions utilized by known partner proteins. The red arrow indicates the cap-binding site with the associated tryptophans in light blue, the purple arrow indicates the positively charge patch, where Importin 8, VPg and EG5 bind with the 2 lysines and the arginine shown. The dorsal surface is also shown and as is the surface used by the NC (non- canonical domain) of eIF4G and 4EBPs with gold yellow arrows (Adapted from [Citation52], PDB3AM7).

Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.