A sequence element downstream of the yeast HTB1 gene contributes to mRNA 3' processing and cell cycle regulation

Histone mRNAs accumulate in the S phase and are rapidly degraded as cells progress into the G(2) phase of the cell cycle. In Saccharomyces cerevisiae, fusion of the 3' untranslated region and downstream sequences of the yeast histone gene HTB1 to a neomycin phosphotransferase open reading frame is sufficient to confer cell cycle regulation on the resulting chimera gene (neo-HTB1). We have identified a sequence element, designated the distal downstream element (DDE), that influences both the 3'-end cleavage site selection and the cell cycle regulation of the neo-HTB1 mRNA. Mutations in the DDE, which is located approximately 110 nucleotides downstream of the HTB1 gene, lead to a delay in the accumulation of the neo-HTB1 mRNA in the S phase and a lack of mRNA turnover in the G(2) phase. The DDE is transcribed as part of the primary transcript and binds a protein factor(s). Maximum binding is observed in the S phase of the cell cycle, and mutations that affect the turnover of the HTB1 mRNA alter the binding activity. While located in the same general region, mutations that affect 3'-end cleavage site selection act independently from those that alter the cell cycle regulation.