CCR4-associated factor 1 coordinates the expression of Plasmodium falciparum egress and invasion proteins |
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Authors: | Balu Bharath Maher Steven P Pance Alena Chauhan Chitra Naumov Anatoli V Andrews Robert M Ellis Peter D Khan Shahid M Lin Jing-Wen Janse Chris J Rayner Julian C Adams John H |
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Institution: | Department of Global Health, College of Public Health, University of South Florida, College of Public Health, 3720 Spectrum Blvd., Suite 304, Tampa, FL, USA. |
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Abstract: | Coordinated regulation of gene expression is a hallmark of the Plasmodium falciparum asexual blood-stage development cycle. We report that carbon catabolite repressor protein 4 (CCR4)-associated factor 1 (CAF1) is critical in regulating more than 1,000 genes during malaria parasites' intraerythrocytic stages, especially egress and invasion proteins. CAF1 knockout results in mistimed expression, aberrant accumulation and localization of proteins involved in parasite egress, and invasion of new host cells, leading to premature release of predominantly half-finished merozoites, drastically reducing the intraerythrocytic growth rate of the parasite. This study demonstrates that CAF1 of the CCR4-Not complex is a significant gene regulatory mechanism needed for Plasmodium development within the human host. |
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