Stabilizing Proteins Using Site Directed RNA Editing

RNA editing is a type of posttranscriptional modification whereby the original RNA sequence of a cell is altered at millions of various points. This mechanism mutates an adenosine nucleotide to an inosine nucleotide, which is recognized by cell machinery as guanine, in specific sites where the RNA adopts a specific secondary structure.

In this project we are interested in manipulating the endogenous process of RNA editing in order to develop a system that will allow protein stabilization in the cell on demand. This can happen by inserting a carefully and computationally engineered oligonucleotide which will construct the necessary structure for the editing to occur. As of now, our goal is to edit a protein’s degron thereby preventing its degradation and leading the protein to be stabilized.

In order to do so we have developed a yeast system that allows us to find the optimal oligonucleotide to insert for the precise editing to occur for each specific target and then allows us to demonstrate the editing activity in a model organism.

This system can be implemented for various uses in addition to the described above. This research can lead to the development of a new generation of medications that are based on alterations in the RNA sequence of a target gene. This type of medications is not limited merely to a small number of proteins and they have the ability to modify a specific function of any target protein.