DSSS - Ribosomes in Gene Regulation: Controlling Protein Diversity Across Cells, Tissues and Organisms

Ribosomes have traditionally been viewed as uniform machines that execute protein synthesis, yet growing evidence suggests that they can act as specialized regulators of gene expression. In this talk, I will discuss how new technologies from our lab have revealed unexpected biological roles for ribosomes in controlling protein diversity across cells and tissues. Using RiboExM and ALIBI, we find that ribosomes are not evenly distributed or compositionally uniform, but instead are spatially organized within cells and developmental contexts, with distinct ribosome-associated proteins and mRNAs linked to specialized cellular functions. These approaches reveal how ribosome organization can shape local translation programs and contribute to cell identity. I will also describe how RiboTweezer, which enables acute and selective depletion of individual ribosomal proteins from mature ribosomes, uncovered a role for a single ribosomal protein ,RACK1, in maintaining cellular pluripotency and regulating the transition from embryonic stem cell states toward neural progenitor programs. Together, these studies support a model in which ribosome heterogeneity and localization provide a dynamic layer of gene regulation that helps determine which proteins are made, where they are made, and in which biological contexts.