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Chapter 2 Control of Gene Expression During the Terminal Differentiation of Erythroid Cells

1975; Elsevier BV; Linguagem: Inglês

10.1016/s0070-2153(08)60025-3

1557-8933

A Fantoni, Mario Lunadei, E Ullu,

RNA modifications and cancer

Sequential differentiative events have three main stages in the differentiation of mammalian erythroid cells: (1) transition from stem cells, (2) committed cells are induced to express the genes for the specialized proteins and become irreversibly committed cells, and (3) terminal differentiation. This chapter discusses the data relative to the differentiation of erythroid cells derived from the yolks sac (YSEC) of fetal mice and describes the basic biochemical aspects of YSEC terminal differentiation. Proteins not directly endowed with the specialized differentiated function, but related to the maintenance of cellular activities, are produced during the early stages of maturation and their synthesis shows an immediate temporal dependence on transcriptional events. The synthesis of specialized proteins, such as hemoglobin, is not dependent on the transcriptional events within a short time interval. During the terminal stages of erythroid differentiation, a continuous decrease of polyribosome content per cell and the reduced availability of mRNAs active for hemoglobin synthesis are observed. The arrest of hemoglobin production is accompanied by the formation of polyribosomes that maintain the aggregated structure but are inactive in protein synthesis. Inactive polyribosomes may not be reactivated in vitro by the addition of any of the factors necessary for protein synthesis. Polyribosome inactivation occurs due to the damage at the 3′OH terminal of the translated mRNA sequence, thus confirming that the availability of messenger molecules directing hemoglobin synthesis is the only factor controlling the extent of hemoglobin gene expression during the terminal differentiation of an erythroid clone.