Incorporation and molecular level consequences of mRNA modifications

Cells face the daunting task of maintaining the right number of proteins, at the right time, under rapidly changing conditions. One way that nature accomplishes this is by chemically modifying DNA, RNA and protein molecules to control their structure, function, stability and localization. A single cell possesses thousands of enzymatically modified RNA sites. These modifications have the potential to directly impact protein production, and disruptions in the RNA modification landscape are associated with an array of diseases including cancers, neurological diseases, and diabetes. Nonetheless, it remains to be discovered how individual sites of modification influence the function of a given RNA. We are working to ascertain how modifications to the molecular blueprints for protein synthesis, messenger RNAs (mRNAs), influence protein production. Our studies have led to the discovery of new mRNA modifications, reframed the current model for RNA modifying enzyme target selection, and identified modifications that change the speed and accuracy of protein synthesis. These findings lay the foundation for establishing complex rules governing the molecular level consequences of mRNA modifications.
Kristin Koutmou