Plasmodium male gametocyte development and transmission are critically regulated by general and transmission-specific members of the CAF1/CCR4/NOT complex

Abstract

19With relatively few known specific transcription factors to control the abundance of specific 20 mRNAs, Plasmodium parasites also regulate the stability and turnover of transcripts to provide 21 more comprehensive gene regulation. Plasmodium transmission stages impose translational 22 38 39 3 AUTHOR SUMMARY 40 Malaria is a disease caused by Plasmodium parasites, which are transmitted during an 41 infectious blood meal by anopheline mosquitoes. Transmission of the sexual stages of the 42 parasite to mosquitoes requires the proper regulation of specific mRNAs. While much work has 43 been done to characterize regulation of mRNAs in female gametocytes, little has been done to 44 assess this regulation in male gametocytes. Here, we demonstrate that PyCCR4-1, a member of 45 the CAF1/CCR4/NOT RNA metabolic complex, acts upon transcripts both directly and indirectly 46 in both male and female parasites, and results in a reduction of male gametocytemia. In 47

Plasmodium Parasites Viewed through Proteomics

“…This is also reflected in the wealth of proteomic studies of this stage, and detailed catalogues of proteins that largely reflect the transcriptional cascade program (listed in Figure 1, Table 1). While analogous synchronization and purification methods exist for rodent-infectious P. berghei and P. yoelii , most studies to date have utilized mixed asexual blood stage parasites to limit vertebrate animal use, and because efficient methods to separate schizonts from gametocytes are lacking [18, 22–24]. While studies of asexual blood stage parasite are important in their own right (all clinical symptoms of malaria are attributed to this stage), many laboratories also use asexual blood stage samples first as they develop new proteomic approaches for Plasmodium , such as quantitative proteomics, surface proteomics, protein/ligand identification, and detection of PTMs (discussed below).…”