RNA functions as an informational, structural and catalytic molecule in cells. However, in most if not all cases where RNA serves as an essential component of a cellular machine, the RNAs collaborate with protein cofactors. Cellular ribonucleoprotein machines for which there is strong evidence that essential active site structures are provided by an RNA include group I and group II introns, RNase P, the spliceosome, the ribosome and telomerase. This non-exhaustive list emphasizes that, although cellular RNA-protein catalysts are relatively rare, they carry out vital processes including RNA biogenesis, polypeptide synthesis and chromosome maintenance. The roles for the protein cofactors have just begun to be explored but include stabilizing and modulating RNA architecture, promoting domain assembly and disassembly, increasing specificity, and allowing regulation.The ultimate goal of this project is to provide insight into the functioning of cellular machines composed of RNA and protein subunits. A one protein-one RNA ribonucleoprotein catalyst composed of the fifth intron of cytochrome b pre-mRNA (the bI5 group I intron) and CBP2 protein (cytochrome b pre-mRNA processing protein 2) from Saccharomyces cerevisiae will serve as a model system. In this simple system, the RNA component contains the active site for the splicing reaction while the protein component enhances the rate of splicing by holding the RNA in its active conformation. The goal of this project is to determine the crystal structure of this simple ribonucleoprotein catalyst. A deeper understanding of this simpler system is likely to yield important generalizations in the broad areas of RNA-protein interactions and protein-facilitated RNA catalysis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES050162-03
Application #
6432364
Study Section
(LSB)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2000
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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