Nicholas Ingolia, Carnegie Institution, Global profiling of translation initiation and protein synthesis
Proteins are the ultimate functional products of most genes, and protein synthesis is a key point of regulation in determining the amount of protein that a cell produces. Translational regulation can also control the production of different protein isoforms from the same transcript and can impact the folding and localization of these protein products. Our appreciation of the full biological impact of translational control has been limited by the difficulty of measuring in vivo translation. We have addressed this challenge by developing ribosome profiling as a technique for monitoring gene expression, globally, at the level of actual protein synthesis. We identified a broad program of translational regulation linked to cell growth, acting in mouse embryonic stem cells as well as in cancer cells, downstream of the mammalian target of rapamycin (mTOR) kinase. Ribosome profiling also revealed unexpected complexity in translation initiation, which likely represents a mechanism controlling protein synthesis. In a few well-studied genes, alternative upstream translation start sites provide transcript-specific control of protein synthesis. Our results suggest that this mechanism could affect many genes, including key regulators of proliferation and pluripotency in ES cells. Alternate sites of translation initiation also yield alternate protein isoforms with distinct and even opposing functions. Ribosome profiling promises to further expand our understanding of the proteins synthesized by the cell and the regulation of their expression.
Location: Carl Icahn Lab 101
Date/Time: 12/04/12 at 3:30 pm - 12/04/12 at 4:30 pm
Category: Special Seminars
Department: Lewis-Sigler Institute