This result provides a strong argument that these two enzymatic activities of CPSF73 are mechanistically distinct and confirms our previous conclusion based on using a different experimental approach that stable binding of the HCC to the core U7 snRNP is critical for CPSF73 to act as an endonuclease but not as a 5′-3′ exonuclease (13,56). Here, CPSF3 is linked to hepatocellular carcinoma.