Our overall goal is to systematically define c/s-regulatory elements in mRNAs that control translation initiation under defined physiological conditions. While the sequence requirements for translation start codon selection have been studied for individual genes, a comprehensive understanding of the rules for start site selection is not known for the human transcriptome.
Our aims are to: A|m 1) Determine translation initiation site usage in human cells in defined physiological states.
Aim 2) Map mRNA structure in vivo and in vitro using chemical probing methods.
Aim 3) Determine the positioning of eukaryotic initiation factor elF3 on mRNAs in human cells.
Aim 4) Develop computational models for predicting start codon selection. Our efforts will initially focus on developing heuristic models for how start codons are selected in human cells. These models will combine the RNA structural information obtained in the above aims with phylogenetic parameters to increase the models'predictive power. As we build a knowledge base for human mRNA structural properties, we will incorporate principles of RNA structure into these models. Our ultimate goal will be to couple general principles of RNA structure to systems-level experimental constraints to enable the prediction of translation initiation patterns in human cells, using minimal new inputs for a given cell type, tissue, or physiological state.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Berkeley
United States
Zip Code
Lee, Yeon J; Wang, Qingqing; Rio, Donald C (2018) Coordinate regulation of alternative pre-mRNA splicing events by the human RNA chaperone proteins hnRNPA1 and DDX5. Genes Dev 32:1060-1074
Costa, Elizabeth A; Subramanian, Kelly; Nunnari, Jodi et al. (2018) Defining the physiological role of SRP in protein-targeting efficiency and specificity. Science 359:689-692
Jost, Marco; Weissman, Jonathan S (2018) CRISPR Approaches to Small Molecule Target Identification. ACS Chem Biol 13:366-375
Horlbeck, Max A; Xu, Albert; Wang, Min et al. (2018) Mapping the Genetic Landscape of Human Cells. Cell 174:953-967.e22
Friedman, Jonathan R; Kannan, Muthukumar; Toulmay, Alexandre et al. (2018) Lipid Homeostasis Is Maintained by Dual Targeting of the Mitochondrial PE Biosynthesis Enzyme to the ER. Dev Cell 44:261-270.e6
Zhang, Yan; Burkhardt, David H; Rouskin, Silvi et al. (2018) A Stress Response that Monitors and Regulates mRNA Structure Is Central to Cold Shock Adaptation. Mol Cell 70:274-286.e7
Wang, Qingqing; Rio, Donald C (2018) JUM is a computational method for comprehensive annotation-free analysis of alternative pre-mRNA splicing patterns. Proc Natl Acad Sci U S A 115:E8181-E8190
Tambe, Akshay; East-Seletsky, Alexandra; Knott, Gavin J et al. (2018) RNA Binding and HEPN-Nuclease Activation Are Decoupled in CRISPR-Cas13a. Cell Rep 24:1025-1036
Li, Bo; Tambe, Akshay; Aviran, Sharon et al. (2017) PROBer Provides a General Toolkit for Analyzing Sequencing-Based Toeprinting Assays. Cell Syst 4:568-574.e7
Iwasaki, Shintaro; Ingolia, Nicholas T (2017) The Growing Toolbox for Protein Synthesis Studies. Trends Biochem Sci 42:612-624

Showing the most recent 10 out of 53 publications