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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI041134-01A2
Application #
2757767
Study Section
Special Emphasis Panel (ZRG1-TMP (03))
Program Officer
Fairfield, Alexandra
Project Start
1999-04-15
Project End
2003-03-31
Budget Start
1999-04-15
Budget End
2000-03-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
Prohaska, Kimberly; Williams, Noreen (2009) Assembly of the Trypanosoma brucei 60S ribosomal subunit nuclear export complex requires trypanosome-specific proteins P34 and P37. Eukaryot Cell 8:77-87
Hellman, Kristina M; Ciganda, Martin; Brown, Silvia V et al. (2007) Two trypanosome-specific proteins are essential factors for 5S rRNA abundance and ribosomal assembly in Trypanosoma brucei. Eukaryot Cell 6:1766-72
Hellman, Kristina; Prohaska, Kimberly; Williams, Noreen (2007) Trypanosoma brucei RNA binding proteins p34 and p37 mediate NOPP44/46 cellular localization via the exportin 1 nuclear export pathway. Eukaryot Cell 6:2206-13
Li, Jinlei; Ruyechan, William T; Williams, Noreen (2003) Stage-specific translational efficiency and protein stability regulate the developmental expression of p37, an RNA binding protein from Trypanosoma brucei. Biochem Biophys Res Commun 306:918-23
Pitula, Joseph; Ruyechan, William T; Williams, Noreen (2002) Two novel RNA binding proteins from Trypanosoma brucei are associated with 5S rRNA. Biochem Biophys Res Commun 290:569-76
Pitula, Joseph S; Park, Jeong; Parsons, Marilyn et al. (2002) Two families of RNA binding proteins from Trypanosoma brucei associate in a direct protein-protein interaction. Mol Biochem Parasitol 122:81-9