CAF40

PF3D7_0507600 (CAF40) is an mRNA-associated component of the CCR4-NOT deadenylase machinery in Plasmodium, functioning within RNA-regulatory ribonucleoprotein complexes across the parasite life cycle (PMID:27381095, PMID:34673764). It was first captured as an mRNA-binding protein present in polysomal fractions of P. falciparum blood stages (PMID:27381095), and in P. yoelii it co-immunoprecipitates with the CCR4-1 deadenylase, establishing its membership in the canonical CAF1/CCR4/NOT complex (PMID:34673764). In P. falciparum it behaves as an RNA-dependent protein that co-sediments with stress granule- and P-body-associated factors including CITH and CAF1 (PMID:38355719), and it co-immunoprecipitates with PfDOZI in both schizonts and gametocytes, marking it as a constituent of P-body-like mRNPs in schizonts and germ cell granule-like mRNPs in gametocytes (PMID:38702310). During gametocytogenesis, CAF40 associates with the RNA-binding protein GD1 within a repressive P-body-like structure, and its protein abundance depends on GD1 homeostasis, being downregulated when GD1 is deleted or overexpressed (PMID:41986327). Beyond these complex-membership and abundance-regulation findings, no dedicated biochemical characterization of CAF40's own molecular activity has been established in the available corpus.

1. 2016 Medium

   Establishing whether CAF40 physically engages mRNA in the parasite addressed whether it participates in post-transcriptional regulation rather than being merely inferred by homology.

   Evidence oligo-dT mRNA interactome capture plus polysome fractionation and MS in P. falciparum blood stages

   PMID:27381095

   Open questions at the time

   • Does not distinguish direct RNA binding from association via complex partners
   • No functional consequence of mRNA association demonstrated
   • Single study, single lab
2. 2021 Medium

   Co-IP of the CCR4-1 deadenylase in a rodent malaria model tested whether CAF40 is a bona fide subunit of the deadenylase complex in Plasmodium.

   Evidence Co-immunoprecipitation of PyCCR4-1 with label-free quantification MS in P. yoelii

   PMID:34673764

   Open questions at the time

   • Direct binary interaction between CAF40 and CCR4-1 not resolved
   • Functional contribution of CAF40 to deadenylase activity not tested
   • Shown in P. yoelii, not P. falciparum
3. 2024 Medium

   Unbiased co-sedimentation and reciprocal-style IP defined the RNP context of CAF40 across life stages, linking it to P-body-like and germ cell granule-like mRNPs.

   Evidence R-DeeP sucrose-gradient co-sedimentation MS and GFP-trap IP of PfDOZI::GFP in P. falciparum schizonts and gametocytes

   PMID:38355719 PMID:38702310

   Open questions at the time

   • Whether CAF40 is required for mRNP assembly is untested
   • No target mRNAs of CAF40 identified
   • Stoichiometry within these granules unknown
4. 2025 Low

   Proximity labeling placed CAF40 near an E3 ubiquitin ligase in immature gametocytes, raising a potential interface between RNA metabolism and the ubiquitin-proteasome system.

   Evidence BioID proximity labeling with MS in P. falciparum immature gametocytes

   PMID:40564933

   Open questions at the time

   • BioID does not confirm direct physical interaction with PfRNF1
   • Functional significance of the proximity unknown
   • Single method, single lab
5. 2026 Medium

   Combining IP with loss- and gain-of-function proteomics showed that CAF40 partners with GD1 in gametocytes and that its abundance is controlled by GD1 homeostasis, linking CAF40 levels to an RNA-binding regulator.

   Evidence IP of GD1-HA-mScarlet with LC-MS/MS plus quantitative proteomics of GD1 deletion and overexpression lines in P. falciparum

   PMID:41986327

   Open questions at the time

   • Mechanism by which GD1 controls CAF40 abundance not defined
   • Whether the GD1-CAF40 interaction is direct is unresolved
   • Functional consequence of altered CAF40 levels not tested

• The intrinsic molecular activity of CAF40, its direct RNA targets, and its specific functional contribution to deadenylation and translational repression remain undefined.
• No CAF40-specific loss-of-function phenotype reported
• No structural or biochemical characterization of CAF40's own activity
• No identified mRNA substrates regulated via CAF40