Funding outcome

Our bodies are made up multiple different cell types that come from the same genetic materials. Each cell type received specific instructions to become a muscle or a brain cell. The instruction is encoded in the genes that will be turned on and made into RNA and then protein. Any disruption in this process will lead to disease development. In the nucleus, genes are organized into tightly wound complexes called chromatin. To turn a gene on, the chromatin has to be opened up by a set of proteins, one of which is called SMARCB1. When SMARCB1 is missing in the brain, a malignant tumor called atypical teratoid rhabdoid tumor (AT/RT) affecting young children will develop. While SMARCB1 is known to be crucial for cellular identity, what is not understood is how and when SMARCB1 protein is made at the right time and in the right cell type. To understand this, we study Snr1 protein in fruit flies, as this protein acts similarly to SMARCB1 in human. We have found that two proteins called Merlin and eIF4E-3 are required to help Snr1 RNA become Snr1 protein. However, we have found that other proteins are also needed so that Merlin and eIF4E-3 can find the Snr1 RNA in the cell. This project will identify and confirm these missing proteins and determine how they help to regulate the process of turning Snr1 RNA into protein. We will look at how changes in Merlin shape will affect Snr1 RNA location in the cell, potentially affect how it will be made into protein. This will tell us how the AT/RT tumors initially form which will assist in development of therapeutic approaches.