Precursor mRNA (pre-mRNA) cleavage factor I(m) (also called NUDIX (nucleoside diphosphate linked moiety X))-type motif 21) is a oligomer composed of a small 25 kDa subunit (CF I(m)25) and a variable larger subunit of either 59, 68 or 72 kDa and plays an important role in pre-mRNA 3'-end cleavage and the selection of poly(A) sites in a 3'-untranslated region (3'-UTR) of mRNA, producing mRNAs with variable 3' ends. The small subunit also interacts with RNA, poly(A) polymerase, and the nuclear poly(A)-binding protein and belongs to the NUDIX hydrolase superfamily. NUDIX hydrolases are found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes.