Plasmodium falciparum cleavage and polyadenylation specificity factor subunit 3 (PfCPSF3) (PfCPSF3)

Plasmodium falciparum cleavage and polyadenylation specificity factor subunit 3 (PfCPSF3) is a 73 kDa zinc-dependent endonuclease that serves as the catalytic core of the CPSF complex in the malaria parasite [1, 6]. It plays an essential role in the 3'-end processing of pre-mRNA by cleaving the transcript downstream of the polyadenylation signal, a prerequisite for polyadenylation and subsequent translation into functional proteins [3, 6]. Because this mRNA maturation process is vital for the survival of P. falciparum across multiple life stages, including the asexual blood stage and liver stage, PfCPSF3 has been identified as a high-priority antimalarial drug target [2, 6]. Small molecule inhibitors, particularly those from the benzoxaborole class such as AN3661 and AN11736, exert potent antimalarial effects by binding to the catalytic site of PfCPSF3 and blocking its enzymatic activity [6, 7]. This inhibition leads to the accumulation of unprocessed mRNA and rapid parasite death, offering a novel mechanism of action that bypasses existing resistance to traditional antimalarials like artemisinin [3, 6]. However, therapeutic development must address the challenge of achieving high selectivity to avoid cross-reactivity with the human CPSF3 ortholog and monitoring for emerging resistance mutations in the parasite's active site [4, 6].

Other names

CPSF3CPSF73CPSF-73mRNA 3'-end-processing endonuclease CPSF3PF3D7_1461800PF14_0364

Inhibition of the endonuclease activity of the CPSF3 subunit, preventing the cleavage and polyadenylation of pre-mRNA, which leads to the failure of mRNA maturation and subsequent parasite death.