Elucidating the Roles of Eukaryotic Initiation Factors Involved in DAP5 Mediated Translation

<p>Translation initiation in eukaryotes is a highly regulated process essential for accurate protein synthesis. It is a dynamic process that involves a complex interplay between messenger RNAs (mRNAs), ribosomal subunits, and a host of initiation factors, ensuring precise start codon selection and the subsequent assembly of the translation machinery. This process has well been known to be mediated by the eukaryotic Initiation Factor (eIF4F), which consists of the cap binding protein eIF4E, the scaffolding protein eIF4GI, and the helicase factor eIF4A.The recognition and binding of eIF4E to the m⁷G cap structure of the mRNA is essential for the subsequent recruitment of eIF4GI and eIF4A to form a translationally active eIF4F complex. During stress conditions in the cell such as hypoxia, nutrient limitation and viral infection, eIF4E is sequestered by 4E-Binding Protein 1 (4E-BP1), a negative regulator of eIF4E activity. As such, the formation of a translationally active eIF4F complex is impaired, leading to a down regulation of translation. The discovery of eIF3d, an alternative cap-binding protein has been a remarkable addition to the field. However, studies on this novel protein are rather limited. In this study, we shed more light on how eIF3d and its direct binding partner DAP5 are able to co-ordinate with each other to drive the cap-dependent but eIF4E independent mechanism of translation of specific mRNA subsets. We present the first known quantitative and mechanistic studies involving the eukaryotic Initiation Factor 3d (eIF3d). The latter half of this manuscript delves into the additional eukaryotic initiation factor requirements of different structured mRNA subsets for DAP5 recruitment. This study adds new dimensions to our understanding of eIF4E independent mechanisms of translation initiation, with insights that may pave the way for future therapeutic interventions. These therapeutic interventions may involve targeting specific steps in this process, offering potential treatments for diseases that may be associated with aberrant protein synthesis.</p>

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Biochemistry

Grantor

The Graduate School and University Center of The City University of New York

Year dc:date.available

2025

Author dc:creator

• Quartey, Jacob NK

Advisor dc:contributor.advisor

• Dixie J. Goss

Committee members dc:contributor.committeemember

• Ruben L. Gonzalez Jr.
• Kevin H. Gardner
• Hualin Zhong
• Akira Kawamura

• Biochemistry
• Bioinformatics
• Biophysics
• Cancer Biology
• Molecular Biology
• Structural Biology
• Hypoxia
• 5 prime untranslated region
• cellular stress
• translation initiation
• eIF4E-independent
• eukaryotic Initiation Factor

Repository record dc:identifier

https://academicworks.cuny.edu/gc_etds/6211

OAI identifier oai:identifier

oai:academicworks.cuny.edu:gc_etds-7334