UC Berkeley

Translation initiation has been regarded as a tightly controlled point of commitment for protein synthesis. Dysregulation of the intricate orchestration of the factors responsible for translation initiation has been shown to be a contributing element in cancer progression, neurological disorders, and many more diseases. Throughout this body of work, we aim to better understand specialized translational regulation which can contribute to transcript selection shifts during times of stress and disease. We not only strive to understand novel non-canonical roles of these translation initiation factors, but also appreciate the unique mechanisms of regulation implemented through the diversification of these factors. We highlight an example of these non-canonical roles through the investigation of eukaryotic initiation factor 3 (eIF3) governed repression of FTL translation. We further this work by demonstrating how disruption of this repression is the molecular cause of a subset of hyperferritinemia cases. Additionally, we establish a platform to better understand the diversity of cap binding complexes and their control over the translatome. We focus on a poorly understood eIF4E1 family member, eIF4E3, and assess its consequences on cellular transformation. These projects aim to widen our appreciation and understanding of translation initiation, its regulation, and specialization under fluctuating environmental conditions.