Translation initiation and dysregulation of initiation factors in rare diseases

Eukaryotic translation is a complex process and is principally regulated at the initiation stage. Alterations in this process can lead to diseased states. In this review, we outline the cap-dependent translation initiation process and discuss the association of dysregulated initiation factors with rare disease conditions. We reviewed 16 rare diseases with defects in translation initiation factors. The ternary complex formation, especially eIF2 activity and mRNA activation, specifically eIF4F complex formation are the most affected steps. Most of the rare diseases affected neuronal tissue followed by endocrine system, suggesting the importance of immediate and direct regulation of protein synthesis in these tissues. Even though the defects in translation initiation factors have been associated with various rare diseases, the precise molecular pathogenesis is not completely understood for all the factors. Understanding the molecular regulation of these initiation factors in different tissues and conditions will enable us to identify diagnostic and prognostic markers for rare diseases and explore new therapeutic interventions.