SRP72

SRP72 (PF3D7_1136400) is one of six polypeptide components of the P. falciparum signal recognition particle (PfSRP) ribonucleoprotein complex, which also contains a 303 nt SRP RNA (PMID:24434517). In blood-stage parasites, SRP72-GFP displays nucleo-cytoplasmic localization, and its nuclear import — together with that of the other PfSRP polypeptides — is mediated by the importin α/β pathway, as evidenced by the ability of ivermectin to block nuclear import at submicromolar concentrations while killing the parasites (PMID:24434517). Beyond its membership in the PfSRP complex and this nuclear-import dependence, no specific molecular function has been established for SRP72 in P. falciparum in the available corpus; it has additionally been detected in the cytosolic interactome of the type II protein arginine methyltransferase PfPRMT5 (PMID:37349497).

1. 2014 Medium

   Establishing that P. falciparum encodes an assembled SRP complex answered whether the parasite possesses this ribonucleoprotein machinery and, unexpectedly, placed SRP72 in the nucleus as well as the cytoplasm, revealing an importin-dependent nuclear-import step exploitable pharmacologically.

   Evidence Transgenic SRP72-GFP parasite lines with fluorescence co-localization microscopy and pharmacological inhibition of importin α/β by ivermectin

   PMID:24434517

   Open questions at the time

   • The specific molecular activity of SRP72 within the PfSRP complex (e.g. contribution to signal-sequence recognition or translocation) is not defined
   • The functional purpose of nucleo-cytoplasmic shuttling and nuclear localization of SRP72 is not established
   • Whether ivermectin acts directly on SRP72 import or on the broader importin pathway is not distinguished for this subunit
2. 2023 Low

   Interactome profiling asked what proteins associate with PfPRMT5 and placed SRP72 among cytosolic candidate interactors, raising the possibility of a regulatory link, though no function of SRP72 itself was tested.

   Evidence Co-immunoprecipitation mass spectrometry of PfPRMT5 in P. falciparum

   PMID:37349497

   Open questions at the time

   • Single Co-IP/MS pulldown with no functional follow-up on SRP72 and no reciprocal validation
   • Whether SRP72 is a direct PfPRMT5 interactor or an indirect co-precipitant is unresolved
   • The transcriptional-regulator role invoked for human SRP68/SRP72 was a hypothesis, not tested for PF3D7_1136400

• The specific molecular function of SRP72 within the PfSRP complex, the biological significance of its nuclear localization, and the reality and consequence of its association with PfPRMT5 remain unresolved.
• No direct assay of SRP72's biochemical role in co-translational targeting or SRP assembly in P. falciparum
• No structural model of PfSRP72 or its contacts within the complex
• No functional consequence established for the SRP72–PfPRMT5 association