Event

Presentation:

Trypanosoma brucei is a protozoan parasite that causes lethal trypanosomiasis in humans and livestock in sub-Saharan Africa. It is a member of the evolutionarily ancient kinetoplastid lineage, which includes other human pathogens such as T. cruzi and Leishmania spp. Kinetoplastids share numerous unusual biological characteristics, one of which is the almost complete absence of transcriptional gene regulation. Rather, gene expression is regulated posttranscriptionally, including major effects at the levels of mRNA stability and translational efficiency. Thus, RNA binding proteins constitute the major gene regulatory factors in these parasites. We discovered DRBD18, an abundant RNA binding protein that is essential for growth of both human bloodstream and insect vector T. brucei life cycle stages. In insect stage T. brucei, DRBD18 depletion significantly impacts the abundance of hundreds of mRNAs. Mass spectrometry shows that DRBD18 interacts with numerous other RNA binding proteins, and both protein-protein interactions and transcriptome regulation are dramatically affected by arginine methylation of DRBD18. Analysis of regulated mRNAs suggests that one DRBD18 function may be to promote or maintain the insect stage of the parasite. Thus, questions that we are currently addressing and whose progress will be discussed here include: What is the effect of DRBD18 in human bloodstream form transcriptome? What are the direct mRNA binding targets of DRBD18 in the two life cycle stages? What are the mechanisms by which DRBD18 impacts mRNA levels? And how are these factors regulated by posttranslational modification of the protein? Together, these studies will provide substantial insight into our understanding of a major gene regulatory protein in a deadly human parasite.

Sara Thomas
Email: coe-gem@buffalo.edu