Abstract
Protein synthesis in eukaryotic cells is a complex, multi-step and tightly regulated process. Translation initiation, the rate limiting step in protein synthesis, is dependent on the activity of eukaryotic translation Initiation Factor 4E (eIF4E). eIF4E is the cap-binding protein which, in synergy with proteins such as the helicase eIF4A and the scaffolding protein eIF4G, binds to mRNA, allowing the recruitment of ribosomes and translation initiation. The function of eIF4E is tightly regulated in cells under normal physiological conditions and can be controlled by post-translational modifications, such as phosphorylation, and by the binding of inhibitory proteins, including eIF4E binding proteins (4E-BPs) and CYFIP1. Recent studies have highlighted the importance of eIF4E in normal or aberrant function of the nervous system. In this mini-review, we will highlight the role of eIF4E function and regulation in the pathophysiology of neurodevelopmental and neuropsychiatric disorders.
Highlights
In Archaea and Bacteria, the mRNA Shine-Dalgarno sequence promotes binding of the ribosome to mRNA and translation initiates (Shine and Dalgarno, 1975)
The majority of eukaryotic precursor mRNAs harbor a 5 end cap, a 7 methylguanosine triphosphate (m7GpppG) structure, which serves as a docking point for eukaryotic translation initiation factors (Furuichi and Miura, 1975; Shatkin, 1976; Furuichi et al, 1977; Sonenberg et al, 1979). eukaryotic translation Initiation Factor 4E (eIF4E) directly binds the mRNA 5 cap (Sonenberg et al, 1979) and interacts with the scaffolding protein eIF4G, which in turn binds the helicase eIF4A to form the eIF4F complex and allow the recruitment of ribosomes to initiate the predominant form of eukaryotic translation: cap-dependent translation (Gingras et al, 1999). eIF4G provides the backbone of the eIF4F complex
The eIF4A helicase unwinds secondary structures present in the mRNA 5 Untranslated Regions (UTRs) to facilitate translation. eIF4A helicase activity is promoted by eIF4G and eIF4B (Gingras et al, 1999), as well as eIF4E (Feoktistova et al, 2013)
Summary
Received: 14 September 2018 Accepted: 06 November 2018 Published: 23 November 2018. Citation: Amorim IS, Lach G and Gkogkas CG (2018) The Role of the Eukaryotic Translation Initiation Factor 4E (eIF4E) in Neuropsychiatric Disorders. Protein synthesis in eukaryotic cells is a complex, multi-step and tightly regulated process. Translation initiation, the rate limiting step in protein synthesis, is dependent on the activity of eukaryotic translation Initiation Factor 4E (eIF4E). The function of eIF4E is tightly regulated in cells under normal physiological conditions and can be controlled by post-translational modifications, such as phosphorylation, and by the binding of inhibitory proteins, including eIF4E binding proteins (4E-BPs) and CYFIP1. Recent studies have highlighted the importance of eIF4E in normal or aberrant function of the nervous system. In this mini-review, we will highlight the role of eIF4E function and regulation in the pathophysiology of neurodevelopmental and neuropsychiatric disorders
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