Cleavage and polyadenylation specificity factor subunit 3 (CPSF3)

Cleavage and polyadenylation specificity factor subunit 3 (CPSF3) is a zinc-dependent endonuclease that serves as the catalytic component of the mRNA 3'-end processing machinery in Trypanosoma cruzi (Source: UniProt Q4D961). In these parasites, mRNA maturation is a unique process where polyadenylation is obligatorily coupled with trans-splicing of the downstream gene, making CPSF3 essential for the production of functional transcripts (Source: Science, 2022, DOI: 10.1126/science.abi8505). The enzyme belongs to the metallo-beta-lactamase superfamily and utilizes two zinc ions in its active site to cleave nascent RNA (Source: Nature Communications, 2017, DOI: 10.1038/s41467-017-01101-x). CPSF3 has been identified as a potent therapeutic target for Chagas disease, particularly for the benzoxaborole class of compounds. The drug candidate AN15368 acts by binding to the CPSF3 active site, effectively blocking its endonuclease activity and leading to a rapid halt in parasite protein synthesis and subsequent cell death (Source: Science, 2022). Because the parasite enzyme exhibits structural differences from the human CPSF3 ortholog, it allows for high selectivity and reduced host toxicity, making it a high-priority target for anti-trypanosomal drug development (Source: ACS Infectious Diseases, 2021).

Other names

CPSF-73TcCPSF3mRNA 3'-end-processing endonuclease CPSF3Cleavage and polyadenylation specificity factor 73 kDa subunit

Inhibition of the endonuclease activity of CPSF3, which prevents the 3'-end cleavage of pre-mRNA and halts parasite protein synthesis.