Cell-cycle related regulation of poly(A) polymerase by phosphorylation

Abstract

THE poly(A) tail found on almost all eukaryotic messenger RNAs^1,2 is important in enhancing translation initiation and determining mRNA stability^3,4. Control of poly (A)-tail synthesis thus has the potential to be a key regulatory step in gene expression and is indeed known to be important during early development in many organisms⁵. To study a possible basis for such regulation, we examined phosphorylation of poly(A) polymerase (PAP) by p34^cdc2/cyclin B (maturation/mitosis-promoting factor, MPF). We show here that PAP can be phosphorylated in vivo and in vitro by MPF. Consistent with this, PAP becomes hyperphosphorylated both during meiotic maturation ofXenopus laevis oocytes and in HeLa cells arrested at M phase, times in the cell-cycle when MPF is known to be active^6,7. We show further that hyperphosphorylation by MPF dramatically reduces the activity of purified PAP, and that PAP isolated from mitotic HeLa cells is similarly inhibited by hyperphosphorylation. This repression probably contributes to the well established reductions in poly (A) ⁺ RNA and/or protein synthesis known to occur in M-phase cells^8–15.