The objective of this proposal is to understand the function and developmental regulation of two highly related nucleic acid binding proteins that we have recently purified and for which we have cloned the genes from the parasitic protozoan, Trypanosoma brucei. These two RNA binding proteins show significant developmental regulation. The larger protein, p37, is produced in the bloodstream form of T. brucei, while the highly related smaller protein, p34, is the predominant form in procyclic T. brucei. We wish to determine the role of these two interesting nucleic acid binding proteins in RNA processing within the cell and the nature of their life cycle dependent regulation.
The specific aims of the project are to: 1. Identify the nucleic acid binding target for p34 and p37. 2. Identify other cellular proteins which associate with p34 or p37. 3. Examine the function of p34 and p37 by genetically altering the expression of the proteins. 4. Determine the nature of the regulation of expression of p34 and p37 [transcriptional, post-transcriptional, or post-translational]. These experimental approaches should lead to a better understanding of the function and significance of these two nucleic acid binding proteins in cellular RNA processing. Given the developmental nature of their expression, we may find them to be critical to the ability of T. brucei to survive transmission from one host type to another. This may provide a strategic target for chemical intervention.
