CAF1

CAF1 (PF3D7_0811300) is a component of the CCR4-NOT deadenylase complex in Plasmodium and acts as a major post-transcriptional regulator coordinating the timing of gene expression during parasite development (PMID:21803864). In P. falciparum, CAF1 governs the expression of more than 1,000 genes across asexual blood-stage development, most prominently those controlling egress and invasion; its loss causes mistimed expression, aberrant accumulation, and mislocalization of egress/invasion proteins, producing premature release of half-finished merozoites and severely reduced intraerythrocytic growth (PMID:21803864). In P. yoelii, expression of only the N-terminal deadenylase domain of CAF1 uncouples the initial coordination of male gametocyte maturation and reduces mosquito infectivity, phenocopying loss of the CCR4-1 subunit and establishing the catalytic deadenylase domain as required for male gametocyte development and host-to-vector transmission (PMID:30703164). Beyond its role as a CCR4-NOT subunit driving timed mRNA regulation in these two contexts, no further biochemical detail—such as direct target mRNAs or reconstituted enzymatic activity—has been characterized for PF3D7_0811300 in the available corpus.

1. 2011 High

   Established that CAF1 is not merely a housekeeping factor but a central timekeeper of blood-stage gene expression, resolving whether post-transcriptional regulation via CCR4-NOT controls the egress/invasion program.

   Evidence Genetic knockout in P. falciparum with transcriptomic profiling, protein localization, and merozoite morphology/growth-rate readouts

   PMID:21803864

   Open questions at the time

   • Direct mRNA targets bound or deadenylated by CAF1 not identified
   • Whether the phenotype reflects CAF1 catalytic activity or a scaffolding role within CCR4-NOT was not separated
   • No structural or biochemical demonstration of deadenylase activity for the P. falciparum protein
2. 2011 Medium

   Placed CAF1 within the CCR4-NOT complex in P. falciparum, positioning it in a defined regulatory pathway rather than acting in isolation.

   Evidence Genetic knockout combined with comparative interactome analysis in P. falciparum

   PMID:21803864

   Open questions at the time

   • Direct physical interactions with other CCR4-NOT subunits not experimentally mapped in this study
   • Stoichiometry and architecture of the Plasmodium complex undefined
3. 2015 Low

   Tested whether the CAF1-CCR4-NOT complex architecture is conserved in P. falciparum, offering a predicted interaction network analogous to the human complex.

   Evidence Bioinformatic interactome/network analysis (Cytoscape); computational prediction only in P. falciparum

   PMID:26525978

   Open questions at the time

   • Prediction only, with no direct experimental validation of CAF1 interactions
   • Analogy to human complex not tested biochemically in the parasite
4. 2019 Medium

   Determined that CAF1's catalytic N-terminal deadenylase domain is functionally required for sexual-stage development and transmission, extending its role beyond asexual growth.

   Evidence Domain-truncation expression construct (N-terminal deadenylase domain only) in P. yoelii with male gametocyte maturation and mosquito infectivity readouts

   PMID:30703164

   Open questions at the time

   • Direct measurement of deadenylase enzymatic activity not shown
   • mRNA targets in male gametocytes not identified
   • Mechanistic link between the domain and CCR4-1 phenocopy not resolved at the molecular level

• The direct mRNA substrates of CAF1, its enzymatic deadenylase activity in vitro, and the physical architecture of the Plasmodium CCR4-NOT complex remain uncharacterized.
• No direct target mRNAs identified
• No reconstituted deadenylase assay for PF3D7_0811300
• Complex composition and subunit contacts experimentally unmapped