You are here: Home News and Events Seminars Biology Spring 2019 Ribosomes in Gene Regulation: Controlling the diversity of proteins that can be produced in specific cells, tissues & organisms

Ribosomes in Gene Regulation: Controlling the diversity of proteins that can be produced in specific cells, tissues & organisms

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Speaker
Maria Barna Assistant Professor of Genetics and of Developmental Biology at Stanford BIO-X
When
26 March 2019 from 3:30 PM to 4:30 PM
Where
8 Mueller Lab
Host
Dept of Biology
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Abstract: In the transmission of biological information, the ribosome has been perceived to serve an integral but largely passive participant in the synthesis of all proteins across all kingdoms of life. Our research has changed this view, by demonstrating that not all of the millions of ribosomes within each cell are the same and that ribosome heterogeneity provides a novel means for diversity of the proteins that can be produced in specific cells, tissues, and organisms. I will present our work centered on developing a roadmap for the characterization of ribosome composition at a single cell level and during cellular differentiation. We employed a highly quantitative mass spectrometry-based approach to precisely quantify the abundance of each ribosomal protein (RP) as well as a large cohort of ~ 400 ribosome associating proteins (RAPs) belonging to actively translating ribosomes. This led to the identification of subsets of ribosomes that are heterogeneous for RP composition. To further address the functional role of ribosome heterogeneity in translational control of the mammalian genome, we employed CRISPR/Cas9 to endogenously tag and purify heterogeneous ribosome populations. We then developed an adapted ribosome profiling method to precisely quantify and characterize the nature of mRNAs translated by distinct heterogenous ribosomes genome-wide. This led to the identification of subpools of transcripts, critical for key cellular processes including cell signaling, metabolism, growth, proliferation and survival, which are selectively translated by specific types of ribosomes. Most interestingly, there are specific signaling pathways where almost every single component is selectively translated by specialized ribosomes demarcated by a single RP. I will further present recent findings on the mechanisms by which ribosome-mediated control of gene expression is encoded by structured RNA elements within 5’UTRs visualized through Cryo-EM. Together, these studies reveal a critical link between ribosome heterogeneity and specialized translational control of the mammalian genome, which adds an important layer of control to the post-transcriptional circuitry of gene regulation.