The Rockefeller University
Host: Marko Jovanovic
Title: Found in Translation: Reprogramming the Translational Landscape in Tumorigenesis
Abstract: The control of translation is a key determinant of protein abundance, which in turn defines cellular states. Increasing evidence implicates that the impact of translational regulation may be even greater during the transition from homeostasis to malignancy. Monitoring the in vivo translational landscape during the transition from homeostasis to malignancy, Dr. Sendoel’s work recently unveiled a hitherto unappreciated role for translational reprogramming involving upstream open reading frames (uORFs). During tumour initiation, the translational apparatus was redirected towards unconventional upstream initiation sites, enhancing the translational efficiency of oncogenic mRNAs. An in vivo RNA interference screen of translational regulators revealed that depletion of conventional eIF2 complexes had adverse effects on normal but not oncogenic growth. Conversely, the alternative initiation factor eIF2A was essential for cancer progression, during which it mediated initiation at these 5’ upstream sites, differentially skewing translation and protein expression. These observations suggest that translational reprogramming involving uORFs constitutes an exciting new frontier in the field of cancer biology and exposes new targets for therapeutic intervention.