SF1

PF3D7_1321700 (SF1) is a Serine/Arginine-rich (SR-type) splicing factor of Plasmodium falciparum that couples pre-mRNA splicing machinery to regulatory phosphorylation (PMID:25188378, PMID:30782661). It is phosphorylated in vitro by all four P. falciparum CLK kinases (PfCLK-1 to -4) specifically on its RS-rich domain, as a peptide lacking this domain is not phosphorylated (PMID:25188378). Consistent with a nuclear RNA-processing role, SF1 localizes predominantly to the nucleus in blood-stage trophozoites and is also detectable in the nucleus of gametocytes (PMID:25188378, PMID:30782661). In P. berghei, the orthologue (PbSR1) associates with nuclear RNA-binding proteins and small nuclear ribonucleoproteins, and unexpectedly also with cytoplasmic rhoptry proteins RhopH1 (Clag3), RhopH2, and RhopH3, with cytoplasmic co-localization of PbSR1 and RhopH2 seen in trophozoites and gametocytes but not in mature schizonts or merozoites (PMID:41634752). Beyond these phosphorylation, localization, and interaction findings, no catalytic mechanism or direct RNA-substrate specificity has been characterized in the available corpus.

1. 2014 Medium

   Establishing whether SF1 is a regulated substrate of the parasite CLK kinase network showed that its RS-rich domain is the specific target of phosphorylation, placing SF1 downstream of PfCLK signalling.

   Evidence in vitro kinase assay with recombinant PfSF-1 and an RS-domain-deletion mutant, P. falciparum

   PMID:25188378

   Open questions at the time

   • in vitro assay only; phosphorylation not demonstrated in living parasites
   • functional consequence of RS-domain phosphorylation on splicing activity untested
   • which PfCLK kinase acts physiologically is not resolved
2. 2014 Medium

   Determining where SF1 acts localized it predominantly to the nucleus in trophozoites and gametocytes, consistent with a role in nuclear RNA processing across asexual and sexual stages.

   Evidence immunofluorescence/imaging localization in asexual blood stages and gametocytes, P. falciparum

   PMID:25188378 PMID:30782661

   Open questions at the time

   • no direct demonstration of association with spliceosomal RNA in P. falciparum
   • does not establish target transcripts or splicing events regulated by SF1
3. 2026 Medium

   Mapping the interactome of the orthologue defined dual associations — with nuclear RNA-binding proteins/snRNPs and, unexpectedly, with cytoplasmic rhoptry proteins — raising the possibility of a role beyond canonical nuclear splicing.

   Evidence IP-MS plus live-cell GFP/mCherry co-imaging in P. berghei ANKA transgenic parasites (PbSR1)

   PMID:41634752

   Open questions at the time

   • rhoptry-protein association shown in P. berghei, not confirmed for P. falciparum SF1
   • functional significance of the cytoplasmic rhoptry interaction unknown
   • IP-MS from a single lab without reciprocal or orthogonal biochemical validation of individual partners

• The direct RNA substrates, the splicing events SF1 controls, and the biological meaning of its cytoplasmic rhoptry-protein associations remain undefined.
• no identified pre-mRNA targets or splicing phenotype from SF1 depletion
• no structural model of SF1 or its RS-domain interactions
• mechanistic link between nuclear splicing role and rhoptry-protein association unexplained