DECAY OF GLOBIN MESSENGER-RNA DURING MEGAKARYOCYTIC DIFFERENTIATION OF ERYTHROLEUKEMIC CELL-LINE IS ACCOMPLISHED THROUGH SHORTENING OF THE POLY(A) TAIL AND DEGRADATION FROM THE 3' END OF THE TRANSCRIPT

Human erythroleukemic cell line K562 normally co-expresses erythroid and megakaryocytic genes, but treatment with an activator of the protein kinase C (PKC), tumor-promoting phorbol ester 12-myristate 13-acetate (PMA) shifts these cells toward megakaryocytic pathway of differentiation. This shift results in silencing of erythroid genes and in additional activation of megakaryocytic genes. It was shown that destabilization of the most abundant erythroid mRNA of K562 cells coding for fetal globin (gamma-globin,) is partially responsible for its silencing in phorbol ester-induced K562 cells. In this work the mechanism of the gamma-globin mRNA destabilization is further investigated. The results show that this process is accompanied by the progressive shortening of the gamma-globin mRNA poly(A) tail. Also, degradation intermediates of gamma-globin mRNA observed during the course of PMA treatment are shown to contain an intact 5' end, but lack the sequences at the 3' end. Based on these findings, a model for the selective destabilization of the erythroid mRNAs during the course of megakaryocytic differentiation of K562 cells is proposed.