PABP

PF3D7_1224300 (PABP1) is a cytoplasmic poly(A)-binding protein that couples poly(A) RNA recognition to both translation initiation and translational repression across the Plasmodium life cycle (PMID:19751846, PMID:20169188). In P. falciparum asexual/general contexts it binds poly(A) RNA specifically in vitro and interacts with the translation initiation factor eIF4G, consistent with a role in the eIF4F initiation complex (PMID:19751846). During sexual development, however, PABP1 is redirected into translationally repressive messenger ribonucleoprotein and stress granule complexes: in P. berghei female gametocytes it is a component of the DOZI/CITH mRNP that stores silenced transcripts and integrates eIF4E and poly(A)-binding protein while excluding eIF4G and P-body degradation factors (PMID:20169188), and in P. falciparum female gametocytes it associates with 7-Helix-1, CITH, and DOZI in stress granules regulating translational repression during gametocytogenesis (PMID:30133543). In P. falciparum male gametocytes PABP1 sits within an MD3-containing post-transcriptional regulatory complex (also including ALBA3, eIF4G, PUF1, NOT1, and CITH) required for male gametocytogenesis (PMID:38148574). The P. yoelii ortholog binds poly(A) strongly, self-associates into RNase-resistant homopolymeric chains, and, beyond its cytoplasmic blood-stage role, localizes to the sporozoite surface and is deposited in gliding trails (PMID:29359180).

1. 2009 Medium

   Establishing whether PABP1 is a bona fide poly(A)-binding protein wired into translation initiation, this work showed specific poly(A) binding and a direct interaction with eIF4G, placing it in the eIF4F initiation complex.

   Evidence In vitro poly(A) binding assay plus co-immunoprecipitation/interaction with eIF4G in P. falciparum

   PMID:19751846

   Open questions at the time

   • No structural mapping of the RNA-binding or eIF4G-interacting regions
   • Functional consequence of the eIF4G interaction on translation not tested in vivo
2. 2010 Medium

   Addressing whether PABP1 also participates in transcript storage rather than only active translation, purification of the female-gametocyte DOZI/CITH mRNP placed PABP1 in a translationally repressive complex that contained eIF4E but excluded eIF4G and degradation factors.

   Evidence Affinity purification and mass spectrometry of the DOZI/CITH mRNP from P. berghei female gametocytes

   PMID:20169188

   Open questions at the time

   • Does not establish whether PABP1 is required for repression or merely co-purifies
   • Mechanism switching PABP1 between eIF4G-bound (active) and eIF4E-bound repressive contexts unresolved
3. 2018 Medium

   To define PABP1's partners in the repressive machinery, reciprocal co-IP placed it in female-gametocyte stress granules with 7-Helix-1, CITH, and DOZI, linking it to translational repression during gametocytogenesis.

   Evidence Co-immunoprecipitation with 7-Helix-1/CITH/DOZI and immunofluorescence localization in P. falciparum female gametocytes

   PMID:30133543

   Open questions at the time

   • Direct versus bridged nature of each interaction not resolved
   • Effect of PABP1 loss on stress granule assembly not tested
4. 2018 Medium

   Testing whether PABP1 has functions beyond RNA regulation, the P. yoelii ortholog was shown to bind poly(A) strongly, self-assemble into RNase-resistant chains, and unexpectedly localize to the sporozoite surface and gliding trails.

   Evidence Multiple poly(A) binding assays, RNase-resistant chain-formation assay, and IFA in P. yoelii

   PMID:29359180

   Open questions at the time

   • Functional role of surface/gliding-trail deposition unknown
   • Whether P. falciparum PABP1 shares the sporozoite surface localization not tested
   • Physiological relevance of in vitro homopolymeric chains unclear
5. 2023 Medium

   Extending PABP1's repressive role to the male lineage, proximity labeling and co-IP placed it in an MD3-anchored complex (ALBA3, eIF4G, PUF1, NOT1, CITH) required for male gametocytogenesis.

   Evidence BioID proximity labeling and co-immunoprecipitation in P. falciparum male gametocytes

   PMID:38148574

   Open questions at the time

   • Individual requirement of PABP1 (versus MD3) for the phenotype not isolated
   • Target transcripts regulated by this complex not defined

• How PABP1 is molecularly switched between the active eIF4G-associated initiation complex and the repressive eIF4E/DOZI/CITH mRNP and stress granules, and what its poly(A)-independent sporozoite-surface role is, remain unresolved.
• No direct loss-of-function of PABP1 itself linking it to any life-cycle phenotype
• No structural model of PABP1 or its complexes
• Regulatory signal governing complex partitioning unknown