Rna15 is a core subunit of cleavage factor IA (CFIA), an essential
transcriptional 3'-end processing factor from Saccharomyces cerevisiae. CFIA is
required for polyA site selection/cleavage targeting RNA sequences that surround
polyadenylation sites in the 3'-UTR of RNA polymerase-II transcripts. RNA
recognition by CFIA is mediated by an RNA recognition motif (RRM) contained in
the Rna15 subunit of the complex. We show here that Rna15 has a strong and
unexpected preference for GU containing RNAs and reveal the molecular basis for
a base selectivity mechanism that accommodates G or U but discriminates against
C and A bases. This mode of base selectivity is rather different to that
observed in other RRM-RNA structures and is structurally conserved in CstF64,
the mammalian counterpart of Rna15. Our observations provide evidence for a
highly conserved mechanism of base recognition amongst the 3'-end processing
complexes that interact with the U-rich or U/G-rich elements at 3'-end
cleavage/polyadenylation sites.