CCR4-associated factor 1 coordinates the expression of Plasmodium falciparum egress and invasion proteins

Eukaryot Cell. 2011 Sep;10(9):1257-63. doi: 10.1128/EC.05099-11. Epub 2011 Jul 29.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Erythrocytes / parasitology*
  • Erythrocytes / pathology
  • Gene Deletion*
  • Gene Expression Regulation
  • Gene Expression*
  • Gene Knockout Techniques
  • Host-Parasite Interactions / genetics*
  • Humans
  • Life Cycle Stages
  • Malaria, Falciparum / parasitology
  • Merozoites / metabolism
  • Oligonucleotide Array Sequence Analysis / methods
  • Plasmodium falciparum / genetics*
  • Plasmodium falciparum / growth & development
  • Plasmodium falciparum / pathogenicity*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Transcription Factors