Cleavage and polyadenylation specificity factor subunit 3 (CPSF3)

Cleavage and polyadenylation specificity factor subunit 3 (CPSF3) is the endonuclease subunit of the cleavage and polyadenylation specificity factor (CPSF) complex, which is essential for the 3'-end processing of precursor mRNA in eukaryotic cells. CPSF3 specifically cleaves RNA at the polyadenylation site and contains a metallo-β-lactamase and β-CASP domain, coordinating two zinc ions necessary for activity. As the key enzyme responsible for producing mature mRNA 3'-termini, CPSF3 is crucial for mRNA maturation, alternative splicing, and regulation of gene expression. Overexpression or inhibition of CPSF3 affects tumor cell survival and has been implicated as a promising therapeutic target in acute myeloid leukemia, Ewing's sarcoma, lung adenocarcinoma, hepatocellular carcinoma, and other cancers. Germline biallelic mutations lead to severe neurodevelopmental syndromes. CPSF3’s essential function and unique enzymatic activity make it a focal point for drug development, mainly through targeted inhibition of its RNA endonuclease activity, but this approach may pose risks of widespread RNA processing defects in normal tissues [2,4,6,7].

Other names

CPSF-73CPSF73cleavage and polyadenylation specific factor 3

Inhibition of CPSF3 endonuclease activity blocks pre-mRNA cleavage, thereby disrupting mRNA maturation and cancer cell proliferation