CELL-CYCLE RELATED REGULATION POLY(A) POLYMERASE BY PHOSPHORYLATION

THE poly(A) tail found on almost all eukaryotic messenger RNAs(1,2) is important in enhancing translation initiation and determining mRNA st ability(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 organisms(5). To study a possible basis for such regulation, we examined phosphorylation of p oly(A) polymerase (PAP) by p34(cdc2)/cyclin B (maturation/mitosis-prom oting factor, MPF). We show here that PAP can be phosphorylated in viv o and in vitro by MPF. Consistent with this, PAP becomes hyperphosphor ylated both during meiotic maturation of Xenopus laevis oocytes and in HeLa cells arrested at M phase, times in the cell-cycle when MPF is k nown to be active(6,7). We show further that hyperphosphorylation by M PF dramatically reduces the activity of purified PAP, and that PAP iso lated from mitotic HeLa cells is similarly inhibited by hyperphosphory lation. This repression probably contributes to the well established r eductions in poly(A)(+) RNA and/or protein synthesis known to occur in M-phase cells(8-15).