Identifying Critical Interactions in the Unique Trypanosoma brucei 5S Ribonucleoprotein Complex and their Role in Ribosome Biogenesis

The eukaryotic parasite Trypanosoma brucei is the causative agent of Human African Trypansomiasis (HAT), which impacts an at-risk population of some 70 million people in sub-Saharan Africa. Current drugs for treating this disease are hindered by significant adverse side-effects, difficult administration, and increasing resistance. One approach for the development of new treatments is to target a process that is both essential and unique to the pathogen.

Ribosome biogenesis is the process of generating mature ribosomes for protein translation. Therefore, disruption of this process is lethal for all organisms. One vital checkpoint in the development of nascent ribosomes is the incorporation of the 5S ribonucleoprotein (RNP) complex. In addition to the components found in other organisms such as Saccharomyces cerevisiae, work in our lab has identified the T. brucei-specific protein P34, which is a unique element of the 5S RNP complex in this organism. P34 directly interacts with other parts of the 5S RNP complex that have been identified in T. brucei, and is vital to maturation of the 60S ribosomal subunit. However, we still do not fully understand its role in the formation and incorporation of the 5S RNP complex into the developing ribosome in T. brucei. Therefore, my work is focused on examining P34 in the context of the 5S RNP complex, and generating a map of its specific interactions and its role in this essential process.

Noreen Williams, PhD