Ribosome biogenesis in the eukaryotic cell

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The ribosome represents a cell's "factory" for making protein and, as such, is an indispensable cellular substructure. A better understanding of this "factory", its function and how it is synthesized is not only of fundamental interest but has many potential applications ranging from biotechnology to medical research. Our research is focused on ribosomal RNA which makes up half the ribosome mass and has been demonstrated to represent the active "machinery" in protein synthesis. We propose to ask further questions about the way the ribosomal RNA is synthesized and assembled into ribosomes as well as how "quality control" is applied to avoid non functional ribosomes that can be very detrimental or even lethal to the cell. Past studies indicate that interactions between the spacer regions in rRNA transcripts are critical to the efficient processing of rRNA as well as ribosome maturation. We have developed a model in which rRNA processing represents a mechanism for quality control during ribosome biogenesis, where the interactions between different regions of the rRNA transcripts help assure that only functional RNAs are incorporated into mature ribosomes. We also have identified a protein complex, a ribosome assembly chaperone (RAC) which interacts with the spacer regions to organize the appropriate processing domain. With further funding we propose to continue our characterization of the RAC protein complex, its sites of interaction within the spacer regions and how it acts to facilitate ribosome biogenesis. Nucleotide modifications also will be examined as a second quality control mechanism and studies will continue on regulatory mechanisms that control ribosome biogenesis. Given the ribosome's central role in cell function and growth, such studies might easily be expected to contribute to human health or agriculture. Many drugs and pesticides, for example, have and will continue to target ribosomes or ribosome synthesis. Graduate students will continue to participate in all aspects of this research in order to provide maximum levels of training