Talk abstracts
Talk on Saturday 10:00-10:15am submitted by Kevin Hart
The CCR4-1 deadenylase plays a major role regulating malarial transmission from host to vector
Kevin J. Hart (Center for Malaria Research, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park), Elyse E. Munoz (Center for Malaria Research, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park), Michael P. Walker (Center for Malaria Research, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park), Dean Taylor (Center for Malaria Research, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park), Mark Kennedy (Center for Malaria Research, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park), Scott E. Lindner (Center for Malaria Research, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park)
Abstract:
The transmission of the malaria parasite between mosquitoes and mammals requires translational repression to ensure that only the proper proteins are expressed at the right time, while still allowing the parasite to prepare the mRNAs it will need for the next developmental stage. With relatively few known specific transcription factors (ApiAP2 family) that may specifically initiate gene transcription, Plasmodium also regulates the stability and turnover of transcripts to provide more comprehensive gene regulation. We and others have demonstrated that the parasite uses both translational repression and transcript degradation mechanisms to achieve this control. Transcript degradation in eukaryotes typically begins with the removal of the Poly-A tail by deadenylases, especially CCR4 and Caf1 that are found in the Caf1-CCR4-Not complex. We have bioinformatically identified four CCR4-domain containing proteins in the Plasmodium yoelii genome that are conserved across Plasmodium species that may provide specialized functions. Genetic deletion of PyCCR4-1, which we found associates with the Caf1-CCR4-Not complex in cytosolic granules, results in significantly fewer exflagellating male gametes and decreased transmission to the mosquito. Comparative RNA sequencing in gametocytes showed a threefold decrease in CDPK4, a known regulator of exflagellation in microgametocytes, along with a decrease in transcripts (e.g. NEK4, CelTOS, PSOP Family) that play important roles in early mosquito stage development and that match the observed phenotypes. It is clear from these data and the work of others that Plasmodium encodes specific deadenylases for the targeted degradation of specific mRNAs to promote and control facets of its development and transmission.
Keywords: CCR4, Translational Repression, Malaria