PLoS pathogens, 2019-01, Vol.15 (1), p.e1007164
2019
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- Autor(en) / Beteiligte
- Titel
- Plasmodium male gametocyte development and transmission are critically regulated by the two putative deadenylases of the CAF1/CCR4/NOT complex
- Ist Teil von
- PLoS pathogens, 2019-01, Vol.15 (1), p.e1007164
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- With relatively few known specific transcription factors to control the abundance of specific mRNAs, Plasmodium parasites may rely more on the regulation of transcript stability and turnover to provide sufficient gene regulation. Plasmodium transmission stages impose translational repression on specific transcripts in part to accomplish this. However, few proteins are known to participate in this process, and those that are characterized primarily affect female gametocytes. We have identified and characterized Plasmodium yoelii (Py) CCR4-1, a putative deadenylase, which plays a role in the development and activation of male gametocytes, regulates the abundance of specific mRNAs in gametocytes, and ultimately increases the efficiency of host-to-vector transmission. We find that when pyccr4-1 is deleted or its protein made catalytically inactive, there is a loss in the initial coordination of male gametocyte maturation and a reduction of parasite infectivity of the mosquito. Expression of only the N-terminal CAF1 domain of the essential CAF1 deadenylase leads to a similar phenotype. Comparative RNA-seq revealed that PyCCR4-1 affects transcripts important for transmission-related functions that are associated with male or female gametocytes, some of which directly associate with the immunoprecipitated complex. Finally, circular RT-PCR of one of the bound, dysregulated transcripts showed that deletion of the pyccr4-1 gene does not result in gross changes to its UTR or poly(A) tail length. We conclude that the two putative deadenylases of the CAF1/CCR4/NOT complex play critical and intertwined roles in gametocyte maturation and transmission.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1553-7374, 1553-7366eISSN: 1553-7374DOI: 10.1371/journal.ppat.1007164Titel-ID: cdi_plos_journals_2251134045
- Format
- –
- Schlagworte
- Animals, Aquatic insects, Binding proteins, Biochemistry, Biology and Life Sciences, Control, Culicidae - metabolism, Disease transmission, DNA binding proteins, Exoribonucleases, Gametocytes, Gametogenesis - physiology, Gene deletion, Gene expression, Gene Expression Regulation, Gene regulation, Genes, Genetic regulation, Homeodomain Proteins, Infections, Infectious diseases, Infectivity, Liver, Malaria, Male, Mass spectrometry, Maturation, Medicine and Health Sciences, Messenger RNA, Methods, Mice, Molecular biology, Mosquito Vectors, Mosquitoes, Parasites, Phenotypes, Plasmodium, Plasmodium - genetics, Plasmodium falciparum - genetics, Plasmodium falciparum - metabolism, Poly(A), Polyadenylation, Polymerase chain reaction, Proteins, Proteomics, Receptors, CCR4 - metabolism, Repressor Proteins, Research and Analysis Methods, Ribonucleases, Ribonucleic acid, Risk factors, RNA, RNA, Messenger - genetics, Scientific imaging, Supervision, Transcription factors, Transcription Factors - metabolism, Transcriptional Activation, Tropical diseases