Human cleavage factor I_m (CFI_m) is a heterodimeric RNA binding protein complex that functions at an early step in the assembly of the pre-mRNA 3′ processing complex. In this report we show that CFI_m can stimulate both cleavage and poly(A) addition, and can act to suppress poly(A) site cleavage in a sequence-dependent manner. Elevated levels of CFI_m suppressed cleavage at the primary poly(A) site of the pre-mRNA encoding the 68 kDa subunit of CFI_m. CFI_m-mediated suppression of poly(A) site cleavage was dependent upon the presence of three copies of an RNA element initially identified by CFI_m-SELEX. These data provide evidence for a mechanism for the regulation of poly(A) site selection by a basal pre-mRNA 3′ processing factor.