Poster abstracts
Poster number 41 submitted by Kevin Hart
Plasmodium Transmission is Critically Regulated by General and Transmission-Specific Deadenylases of the CAF1/CCR4/NOT Complex
Kevin J. Hart (Department of Biochemistry and Molecular Biology, Center for Malaria Research, Pennsylvania State University, University Park, Pennsylvania 16802), Jenna Oberstaller (Center for Global Health and Infectious Diseases Research, Department of Global Health, University of South Florida, 3720 Spectrum Blvd, Suite 404, Tampa, Florida 33612 ), Michael P. Walker, Mark F. Kennedy (Department of Biochemistry and Molecular Biology, Center for Malaria Research, Pennsylvania State University, University Park, Pennsylvania 16802), Ian Padykula (Center for Global Health and Infectious Diseases Research, Department of Global Health, University of South Florida, 3720 Spectrum Blvd, Suite 404, Tampa, Florida 33612 ), John H. Adams (Center for Global Health and Infectious Diseases Research, Department of Global Health, University of South Florida, 3720 Spectrum Blvd, Suite 404, Tampa, Florida 33612 ), Scott E. Lindner (Department of Biochemistry and Molecular Biology, Center for Malaria Research, Pennsylvania State University, University Park, Pennsylvania 16802)
Abstract:
With relatively few known specific transcription factors (ApiAP2 family), Plasmodium parasites regulate the stability and turnover of transcripts to provide more comprehensive gene regulation. However, few proteins that impose translational repression in Plasmodium sexual stages are known, and those that are characterized primarily affect female gametocytes. We have characterized CCR4-1 of the CAF1/CCR4/NOT complex, which we show plays a role in activating male gametocytes, stabilizing transcripts in gametocytes, and regulating host-to-vector transmission. Comparative RNA-seq demonstrates that many transcripts important for these functions are affected. In contrast, genetic deletion of the major deadenylase CAF1 is lethal, yet expression of the N-terminal CAF1 domain is permissive but prevents complex assembly and phenocopies the ccr4-1 deletion. Transgenic P. falciparum parasites expressing a similar CAF1 disruptant supports this data. We conclude that the general and transmission-specialized deadenylases of the CAF1/CCR4/NOT complex play critical and intertwined roles in parasite growth and transmission.
Keywords: CCR4, Translational Repression, Plasmodium