Cleavage factor I m (CFI m ) is a highly conserved component of the eukaryotic mRNA 3′ processing machinery that functions in sequence-specific poly(A) site recognition through the collaboration of a 25 kDa subunit containing a Nudix domain and a larger subunit of 59, 68, or 72 kDa containing an RNA recognition motif (RRM). Our previous work demonstrated that CFI m 25 is both necessary and sufficient for sequence-specific binding of the poly(A) site upstream element UGUA. Here, we report the crystal structure of CFI m 25 complexed with the RRM domain of CFI m 68 and RNA. The CFI m 25 dimer is clasped on opposite sides by two CFI m 68 RRM domains. Each CFI m 25 subunit binds one UGUA element specifically. Biochemical analysis indicates that the CFI m 68 RRMs serve to enhance RNA binding and facilitate RNA looping. The intrinsic ability of CFI m to direct RNA looping may provide a mechanism for its function in the regulation of alternative poly(A) site selection.