RPS21

PF3D7_1144000 (RPS21) is a structural component of the small (40S) subunit of the P. falciparum 80S ribosome, established by cryo-EM structures of the native ribosome that resolved the 40S ribosomal protein complement, including RPS21, and distinguished the parasite ribosome from its mammalian counterpart (PMID:24913268, PMID:26432834). In situ cryo-electron tomography of P. falciparum-infected erythrocytes has since visualized the 40S subunit containing RPS21 within actively translating native ribosomes in the cellular context (PMID:40825879). Beyond its membership in the 40S small subunit, no experiment in the available corpus has established a specific catalytic, regulatory, or functional role for RPS21 itself.

1. 2014 Medium

   Whether RPS21 is part of the parasite ribosome and how the P. falciparum small subunit is organized was unresolved; a high-resolution structure was needed to place RPS21 within the assembled ribosome.

   Evidence Cryo-EM structure at 3.2 Å of the P. falciparum 80S ribosome bound to emetine, resolving the 40S protein complement

   PMID:24913268

   Open questions at the time

   • No functional experiment specific to RPS21 was performed; its role is inferred only from complex membership
   • Does not establish whether RPS21 has any activity distinct from structural scaffolding
2. 2015 Medium

   Whether the placement of RPS21 in the 40S subunit was robust and how the parasite ribosome differs structurally from the mammalian ribosome required independent reconstructions.

   Evidence Multiple cryo-EM reconstructions of native schizont-stage ribosomes with atomic model building, confirming RPS21 as a 40S component

   PMID:26432834

   Open questions at the time

   • No RPS21-specific functional or genetic perturbation performed
   • Dynamic features attributed to the ribosome as a whole, not to RPS21 in particular
3. 2025 Medium

   Whether the RPS21-containing 40S subunit occupies its structural position within ribosomes engaged in translation inside intact parasites, rather than only in purified preparations, was addressed by imaging ribosomes in situ.

   Evidence In situ cryo-electron tomography of P. falciparum-infected erythrocytes yielding eight high-resolution structures of native translating ribosomes, with and without a Plasmodium-specific translation inhibitor

   PMID:40825879

   Open questions at the time

   • RPS21 was visualized only as part of the global 40S subunit; no function was assigned to it
   • Translation-state and biogenesis changes describe the ribosome broadly, not RPS21 specifically

• Whether RPS21 contributes any specific function to 40S assembly, mRNA/tRNA handling, or translational regulation beyond being a structural constituent of the small subunit remains unaddressed.
• No genetic knockout, knockdown, or depletion of RPS21 reported
• No interaction or substrate mapping distinguishing RPS21 from the bulk 40S subunit
• No evidence for a role in ribosome biogenesis specific to RPS21