CELF1

CELF1 (PF3D7_1359400) is a bona fide RNA-binding protein of Plasmodium that participates in post-transcriptional RNA regulation across the parasite life cycle (PMID:25447287, PMID:27381095). In P. falciparum it binds RNA directly in vitro by UV-crosslinking and EMSA — an activity absent from its paralog CELF2 under identical conditions (PMID:25447287) — and is captured on mRNA in vivo by oligo-dT interactome capture (PMID:27381095). During asexual blood stages it associates with a large mRNA repertoire (~1376 features from ~1040 mRNAs) enriched for a UG-rich motif resembling the intronic CELF-family binding motif of other species, consistent with a role in pre-mRNA splicing regulation (PMID:25447287), and the GFP-tagged protein distributes between the nucleus and cytoplasm in a manner indicative of nucleocytoplasmic shuttling (PMID:25447287). CELF1 further engages translational-control machinery in a stage-specific fashion: in P. falciparum schizonts it co-immunoprecipitates with PfDOZI-associated stress granule-like mRNPs containing eIF4A, eIF4E, PABP1, Alba and ribosomal proteins (PMID:38702310), and in P. yoelii it is a proximity interactor of ALBA4 within the DOZI/CITH/ALBA translational control complex specifically in female gametocytes but not zygotes (PMID:39777415). Beyond these binding and association data, the functional consequences of CELF1's RNA binding — including any direct role in splicing or translational repression — have not been characterized in the available corpus.

1. 2014 Medium

   Whether PF3D7_1359400 is a genuine RNA-binding protein was unknown; direct biochemistry established that it binds RNA and distinguished it from its non-binding paralog.

   Evidence UV-crosslinking and EMSA with 12-mer RNAs, comparing CELF1 and CELF2 in P. falciparum

   PMID:25447287

   Open questions at the time

   • No independent replication of the in vitro binding assay
   • Sequence specificity and affinity not quantified
   • No structural basis for the CELF1 vs CELF2 difference
2. 2014 Medium

   The subcellular compartment in which CELF1 acts was unknown; GFP tagging showed dual nuclear/cytoplasmic distribution, consistent with nucleocytoplasmic shuttling and dual-compartment function.

   Evidence GFP-tagged transgenic P. falciparum live-cell imaging in asexual stages

   PMID:25447287

   Open questions at the time

   • Cell-to-cell variability in distribution not mechanistically explained
   • Shuttling signals or regulatory triggers not identified
   • Single lab, no independent confirmation
3. 2014 Medium

   The RNA targets of CELF1 and its likely regulatory role were undefined; ribonomics identified a large bound mRNA set and a UG-rich intronic-type motif, implicating CELF1 in pre-mRNA splicing regulation.

   Evidence RNA immunoprecipitation coupled to DNA microarray with motif analysis in P. falciparum asexual stages

   PMID:25447287

   Open questions at the time

   • No functional validation of a splicing role
   • Direct vs indirect binding to targets not distinguished
   • Motif not experimentally confirmed as the binding determinant
4. 2016 Medium

   Whether CELF1 binds mRNA inside living parasites (not only in vitro) was unresolved; interactome capture confirmed in vivo mRNA association.

   Evidence Oligo-dT mRNA interactome capture with quantitative mass spectrometry in P. falciparum blood stages

   PMID:27381095

   Open questions at the time

   • Does not identify which mRNAs are bound in vivo
   • No link between capture and a specific regulatory outcome
5. 2024 Medium

   Whether CELF1 participates in higher-order mRNP assemblies was unknown; Co-IP placed it within PfDOZI-associated stress granule-like mRNPs in schizonts alongside translational regulators.

   Evidence GFP-trap immunoprecipitation of PfDOZI::GFP followed by mass spectrometry in P. falciparum schizonts

   PMID:38702310

   Open questions at the time

   • Single Co-IP without reciprocal validation
   • Direct vs RNA-bridged association not resolved
   • CELF1's specific function within the granule not tested
6. 2024 Low

   Whether CELF1 belongs to a defined protein complex was addressed by IP-MS and gradient co-segregation, indicating co-purification with an RNA-binding protein but likely membership in multiple distinct complexes.

   Evidence IP-MS and sucrose-gradient R-DeeP with PF3D7_0823200 in P. falciparum 3D7 asexual stages

   PMID:38355719

   Open questions at the time

   • Low co-segregation correlation (−0.67) suggests indirect or complex-dependent association not independently confirmed
   • Single Co-IP experiment
   • Composition of the distinct complexes not defined
7. 2025 Medium

   Whether CELF1 engages translational-control machinery in transmission stages was unknown; proximity proteomics placed it in the DOZI/CITH/ALBA complex specifically in female gametocytes.

   Evidence TurboID proximity labeling of DOZI and ALBA4 in P. yoelii female gametocytes versus zygotes

   PMID:39777415

   Open questions at the time

   • Stage-dependent interaction not functionally validated
   • Shown in P. yoelii; not confirmed for P. falciparum gametocytes
   • Proximity does not establish direct binding

• The direct functional consequence of CELF1 RNA binding — whether it regulates pre-mRNA splicing, mRNA stability, or translational repression — remains undetermined.
• No loss-of-function or genetic knockout phenotype reported
• No demonstrated effect on splicing of target transcripts
• Direct RNA targets in vivo not mapped at nucleotide resolution