RAD21

RAD21 (PF3D7_1440100) is identified as a core subunit of the cohesin complex in Plasmodium falciparum, together with its partner subunit SMC3 (PMID:37592911). In the available corpus, all functional experiments were performed on the SMC3 subunit rather than on RAD21 itself: ChIP-seq showed SMC3 occupancy at promoters of stage-specific genes during the intraerythrocytic developmental cycle, where its enrichment inversely correlates with gene expression and chromatin accessibility, and SMC3 knockdown de-represses egress- and invasion-associated genes normally expressed at later stages, indicating that the cohesin complex contributes to transcriptional repression of stage-specific genes (PMID:37592911). Beyond its membership in the cohesin complex, no direct functional or mechanistic experiment has been performed on RAD21 (PF3D7_1440100) in the available corpus.

1. 2023 Low

   It was unknown whether the P. falciparum cohesin complex regulates gene expression during the asexual cycle; this work established that cohesin (assayed via SMC3) represses stage-specific genes, and placed RAD21 within that complex as a core subunit.

   Evidence ChIP-seq and conditional SMC3 knockdown with chromatin accessibility assays during the intraerythrocytic developmental cycle

   PMID:37592911

   Open questions at the time

   • No experiment was performed directly on RAD21 (PF3D7_1440100); its individual contribution to the repressive function is not established.
   • The mechanism by which cohesin represses transcription (loop extrusion, promoter occlusion, or otherwise) is not resolved.
   • RAD21 localization, essentiality, and interaction interface within P. falciparum cohesin are uncharacterized.

• What RAD21 (PF3D7_1440100) itself contributes to cohesin function in P. falciparum remains unknown, as no direct RAD21 perturbation, localization, or interaction experiment exists in the corpus.
• No RAD21-specific knockdown/knockout phenotype.
• No direct evidence that RAD21 co-occupies the SMC3-bound promoters.
• No structural or biochemical characterization of RAD21 within the P. falciparum cohesin complex.