Wed, Apr. 6, 2022, 4:30pm
Taylor Auditorium, Frick Chemistry Laboratory
Host: Ralph Kleiner
Incorporation and molecular level consequences of uridine mRNA modifications.
Cells face the daunting challenge of synthesizing the correct number of proteins at the right time with high fidelity. Messenger RNAs (mRNAs) serve as the blueprints for protein synthesis by the ribosome, and the post-transcriptional modification of mRNA presents one avenue for cells to regulate protein production. The recent discovery of mRNA chemical modifications has generated tremendous excitement because these modifications have the potential to regulate mRNA function and control protein expression levels. Pioneering work on mRNA modifications have implemented sequencing-based methods to map the location of individual chemical modifications across all of the RNA molecules in a cell. Despite a rapidly growing recognition of their importance, fundamental questions regarding the identity, prevalence and functional consequences of mRNA modifications remain to be answered. We are working to fill these critical knowledge gaps and establish a quantitative and mechanistic basis for understanding how mRNA chemical modifications impact protein synthesis at the molecular level. The work presented here demonstrates the consequences of modifying individual uridine nucleobase positions on the speed and accuracy of the ribosome, and presents evidence suggesting a new framework for conceptualizing how key uridine modifying enzymes (pseudouridine synthases) select their mRNA targets.