Two different machineries are involved in the 3'-end processing of mRNA precursors (pre-mRNAs). Most eukaryotic pre-mRNAs  are  cleaved  and  then  polyadenylated at  the  3¢-end, and  their processing  machinery  (the canonical n1achinery) is composed of CPSF (cleavage and polyadenylation specificity factor), CstF (cleavage stin1ulation factor), poly(A) polymerase (PAP), CF I (cleavage factor I), CF II, RBBP6, and other protein factors, with a total molecular weight of about 1.8 MDa. In comparison, metazoan replication-dependent histone pre-mRNAs are cleaved at the 3'-end but are not polyadenylated, and their processing machinery is the U7 snRNP, with a total molecular weight of about 1 MDa. CPSF73 is the endoribonuclease for the cleavage reaction in both machineries, and 

recent studies suggest CPSF73 is also a potential target for novel anti-cancer drugs.

We have been studying the molecular  basis for the functions of these machineries, and have determined  the structures of their protein factors and sub-complexes over the years, including the recent structure of a reconstituted, active U7 snRNP in complex with a model histone pre-mRNA substrate, with the machinery poised for the cleavage reaction. This structure has provided unprecedented molecular insights into pre-mRNA 3'-end processing.