A compensatory link between cleavage/polyadenylation and mRNA turnover regulates steady-state mRNA levels in yeast

Cells have compensatory mechanisms to coordinate the rates of major biological processes, thereby permitting growth in a wide variety of conditions. Here, we uncover a compensatory link between cleavage/polyadenylation in the nucleus and mRNA turnover in the cytoplasm. On a global basis, same-gene 3' mRNA isoforms with > two-fold differences in half-lives have steady-state mRNA levels that differ by significantly less than a factor of two. In addition, increased efficiency of cleavage/polyadenylation at a specific site is associated with reduced stability of the corresponding 3' mRNA isoform. This inverse relationship between cleavage/polyadenylation and mRNA isoform half-life reduces the variability in the steady-state levels of mRNA isoforms, and it occurs in all four growth conditions tested. These observations suggest that during cleavage/polyadenylation in the nucleus, mRNA isoforms are marked in a manner that persists upon translocation to the cytoplasm and affects the activity of mRNA degradation machinery, thus influencing mRNA stability. Overall design: We have examined mRNA isoform stability by using 3' READS to measure mRNA 3' isoform levels after Rpb1 depletion in four different growth media.