Discovery and characterization of conserved binding of eIF4E 1 (CBE1), a eukaryotic translation initiation factor 4E–binding plant protein

Abstract

In many eukaryotes, translation initiation is regulated by proteins that bind to the mRNA cap-binding protein eukaryotic translation initiation factor 4E (eIF4E). These proteins commonly prevent association of eIF4E with eIF4G or form repressive messenger ribonucleoproteins that exclude the translation machinery. Such gene-regulatory mechanisms in plants, and even the presence of eIF4E-interacting proteins other than eIF4G (and the plant-specific isoform eIFiso4G, which binds eIFiso4E), are unknown. Here, we report the discovery of a plant-specific protein, conserved binding of eIF4E 1 (CBE1). We found that CBE1 has an evolutionarily conserved eIF4E-binding motif in its N-terminal domain and binds eIF4E or eIFiso4E CBE1 thereby forms cap-binding complexes and is an eIF4E-dependent constituent of these complexes Of note, plant mutants lacking CBE1 exhibited dysregulation of cell cycle-related transcripts and accumulated higher levels of mRNAs encoding proteins involved in mitosis than did WT plants. Our findings indicate that CBE1 is a plant protein that can form mRNA cap-binding complexes having the potential for regulating gene expression. Because mammalian translation factors are known regulators of cell cycle progression, we propose that CBE1 may represent such first translation factor-associated plant-specific cell cycle regulator.

A Novel Interaction Network Used by Potyviruses in Virus–Host Interactions at the Protein Level

“…For example, different animal-infecting picornaviruses control nucleocytoplasmic trafficking by targeting nuclear pore proteins and transport factors [77]. The recently found plant protein CBE1 with a 4E-binding motif can control the expression of nuclear-encoded genes and was proposed to be the first characterized translation factor associated with plant-specific cell cycle regulators [22]. As both PVA VPg and HCpro contain a functional 4E-binding motif, they may compete with this plant factor to affect gene regulation.…”

“…Plants lack 4E-binding protein homologs; however, a plant-specific protein, conserved binding of eIF4E 1 (CBE1), which contains a 4E-binding motif, was recently identified. CBE1 is a constituent of 4E cap-binding complexes and has the potential to regulate gene expression [22]. Plant 4Es can also be phosphorylated at the lateral surface of 4E by the energy-sensing kinase SnRK1, which inhibits translation [23].…”

Translational gene regulation in plants: A green new deal

“…In contrast, the plant host can utilize multiple paralogs, in keeping with the finding that more than one eIF4F gene must be lost before mutants suffer serious detrimental phenotypes (Callot & Gallois, 2014;Gallie, 2016;Gauffier et al, 2016;Lellis et al, 2019;Q. Li et al, 2017;Patrick et al, 2018). Virus resistance can evolve when the paralog serving the virus mutates to a loss-offunction allele.…”

“…CBE1 bears hallmarks of TOR signaling, given that its phosphorylation is induced by sucrose and rapidly reduced by the TOR inhibitor AZD-8055 (Van Leene et al, 2019). Moreover, CBE1 attenuates expression of cell cycle genes (Patrick et al, 2018). While the effect of CBE1 and other proposed eIF4E-binding proteins on translation remains open (Z.…”

“…m 6 A is expected to alter the F I G U R E 6 Translational control by proteins associated with the eIF4 cap-binding complex. CBE1 is an eIF4E-binding protein that is phosphorylated in a TOR-dependent manner (Patrick et al, 2018). CERES likewise forms cap-binding complexes with eIF4E/iso4E, which lack eIF4G/iso4G (Toribio et al, 2019).…”