On the Cutting Edge: Regulation and Therapeutic Potential of the mRNA 3′ End Nuclease

Cleavage of nascent transcripts is a fundamental process for eukaryotic mRNA maturation and for the production of different mRNA isoforms. In eukaryotes, cleavage of mRNA precursors by the highly conserved endonuclease CPSF73 is critical for mRNA stability, export from the nucleus, and translation. As an essential enzyme in the cell, CPSF73 surprisingly shows promise as a drug target for specific cancers and for protozoan parasites. In this review, we cover our current understanding of CPSF73 in cleavage and polyadenylation, histone pre-mRNA processing, and transcription termination. We discuss the potential of CPSF73 as a target for novel therapeutics and highlight further research into the regulation of CPSF73 that will be critical to understanding its role in cancer and other diseases.