Grant: Operating Grant

When a gene is expressed, several events have to be coordinated. First, the stretch of DNA encoding that gene has to be transcribed into a messenger molecule, the RNA. This RNA molecule then needs to be modified in order to insure its stability and to refine the message that is to be delivered. The RNA then moves out of the nucleus where it is decoded (or translated) to make a protein. All these molecular events have to occur in a highly coordinated manner. The enzyme that is responsible for the first step (the RNA polymerase II) is the conductor of the whole gene expression process. It contains a domain (the CTD) that sequentially binds the enzymes and other proteins required for the process to be tightly coordinated. Without the CTD, the RNA is not processed properly and is degraded. Consequently, cells can not survive without the CTD. In order for gene expression to be orchestrated, the CTD undergoes a series of reversible chemical modifications each time a gene is being expressed. These modifications are the ones that allow the CTD to bind to such a large number of different proteins. In this proposal, we aim 1) to identify more proteins capable of binding the CTD and regulating gene expression; 2) to better understand the role of a newly identified CTD-binding protein that has the capacity to modify an important transcription factor; 3) to further understand how the CTD is modified.