Grant: Discovery Grants Program - Individual

Ribosomes are molecular machines found in all cells. They play an essential role as they link the genome (or DNA) to proteins. Ribosomes "read" the language of genetics and translate it into the language of proteins. In turn, proteins give cells architectural and structural support, giving shape to our bodies, and promote the chemical reactions that convert food into energy and allow us to use that energy for movement, growth, and development. We understand how ribosomes read genetic information and translate it into protein, much as we understand the working of a car engine. However, we have a poor understanding of the complex production line by which ribosomes are assembled. The proposed research examines how the ribosome is assembled and investigates another molecular machine, called the SSU processome, which assembles part of the ribosome - to continue with the automotive comparison - the SSU processome acts as part of the assembly line in car manufacturing. More specifically, we are proposing to investigate a poorly understood SSU processome protein called Emg1 and the role that it plays in the assembly of the region of the ribosome that reads and translates genetic information, one of the most important functions of the ribosome. Ribosomes are assembled from RNA, a close cousin of DNA, and contain many proteins. Much like car assembly, the ribosomal RNA must be made and cut to size as it is being folded, and as other parts (such as proteins) are being added. The proposed Objective 1 will determine Emg1's role in removing previous assembly line components, here called snoRNAs, from the ribosome during assembly. Failure to remove snoRNAs likely blocks later ribosome assembly steps from occurring. In Objective 2, we will catalogue the protein parts and identify the connections between the parts of a new ribosome assembly robot in the SSU processome, the Emg1 subcomplex. This robot is important because it assembles the region of the ribosome that reads and translates genetic information into proteins. If this region is mis-assembled, the ribosome may be slow or make errors in reading and translating genetic information into proteins. These Objectives will answer major ribosome assembly questions. Objective 2 will define the protein parts and connections of the novel Emg1 assembly line component while Objective 1 will determine the mechanism by which Emg1 functions in removing specific snoRNAs from assembling ribosomes. This work will greatly benefit all Canadians. The assembly of ribosomes is an important process in all cells. It influences all of biology, from ecology to human health (such as all cancers and many genetic disorders) to agriculture. This research will increase our understanding of ribosome assembly, a fundamental component of cell growth and division. In turn, this may allow us to manipulate ribosome assembly to increase crop and livestock production and to intervene when ribosome assembly becomes defective in disease.