The objective of this proposal is to further characterize the function and developmental regulation of two highly related nucleic acid binding proteins, p34 and p37, from the parasitic protozoan, Trypanosoma brucei. We have recently shown that these proteins are associated with 5 S rRNA. We have further shown that these proteins also interact with a family of nucleolar proteins, the NOPP44/46 proteins. These two RNA binding proteins show significant developmental regulation and although the proteins are highly homologous they are regulated by different mechanisms, p34 is predominantly expressed in procyclic forms and is regulated at the level of mRNA stability, p37 is predominantly expressed in the bloodstream stage and is regulated by translational control and protein stability.
The specific aims of the project are to: 1. Determine whether the two homologous RNA binding proteins, p34 and p37, have distinct roles in the trypanosome, particularly in light of their differential regulation. 2. Determine the mechanism of posttranscriptional regulation for the expression of the p34 protein. 3. Determine the mechanisms of translational regulation of expression for the p37 protein. These experimental approaches will lead to a better understanding of the function and significance of these two unique 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.
| 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 |
