Essential Yeast Protein with Unexpected Similarity to Subunits of Mammalian Cleavage and Polyadenylation Specificity Factor (CPSF)

Abstract

The 3′ ends of most eukaryotic messenger RNAs are generated by internal cleavage and polyadenylation. In mammals, there is a strict dependence of both reactions on the sequence AAUAAA, which occurs upstream of polyadenylation [poly(A)] sites and which is recognized by CPSF. In contrast, cis-acting signals for yeast 3′-end generation are highly divergent from those of mammals, suggesting that trans-acting factors other than poly(A) polymerase would not be conserved. The essential yeast protein Brr5/Ysh1 shows sequence similarity to subunits of mammalian CPSF and is required for 3′-end processing in vivo and in vitro. These results demonstrate a structural and functional conservation of the yeast and mammalian 3′-end processing machineries despite a lack of conservation of the cis sequences.