Protein synthesis is a critical integration point for cellular metabolism, growth, and gene expression. The amino acid building blocks for new protein synthesis can become directly limiting for the ribosome if they become scarce in the cell’s microenvironment, a condition observed across normal and disease physiology. As charged tRNA levels fall, ribosomes stall, collide, and prematurely fall-off at specific codons. These events have been linked to phenotypes from bacterial biofilm formation to cancer progression, raising the possibility that they represent an ancient, direct mechanism for tuning gene expression across different metabolic environments. We seek to understand the mechanisms and regulators behind ribosome stalling and fall-off in nutrient limited cancer cells, and the effects of pressing this translational “eject” button on basic cell function and disease progression.
