Grant: Operating Grant

The messages from our genome that direct cellular function are encoded in RNA. These messages (called mRNA) not only contain instructions on how to build a specific protein but also instructions on where, when, and how many copies of that protein to build. Though we already know the genetic code that describes how to translate the RNA message into its associated protein product, we still do not know how to read the other instructions, those that regulate the production of the protein, encoded in the mRNA. Deciphering the RNA regulation code is important. Many inherited diseases appear to be caused by genetic mutations in RNA regulatory instructions. Furthermore, knowing the RNA regulation code may provide us with new strategies for treating disease by targeting aspects of mRNA regulation. We propose to decipher this regulation code in two steps. First, we will learn the "words" of the code by analyzing the binding preferences of the regulatory proteins that bind to mRNA. Then, we will decipher the "grammar" of the code by using computer algorithms that learn to predict the localization and stability of an mRNA based on the sequence of code words it contains. We will validate our predictions by manipulating what we believe to be the regulatory instructions in particular mRNAs, and ensure that our predictions on how the regulation changes match reality. We will carry out this research in fruit flies (Drosophila) because the regulatory code is likely to be similar between fruit flies and human, but there is readily available data on mRNA regulation in fruit flies that is unavailable in humans.