Processing of p53 mRNA during induced differentiation of murine erythroleukemia cells: is an altered splicing mechanism responsible for the post-transcriptional control of gene expression?

Abstract

Our recent findings [Khochbin et al.,J. Mol. Biol. 200 (1988) 55–64] have demonstrated a dramatic decrease in the p53 protein and mRNA early after induction of differentiation in murine erythroleukemia cells. When investigating regulatory mechanisms of the p53 mRNA down-regulation, we have found a post-transcriptional control for the mRNA accumulation during the first hours of induced differentiation. Using a cell-fractionation procedure, we have attempted to localize the cellular compartment involved m the induced post-transcriptional process that controls the amount of mature p53 mRNA during differentiation. Our results agree well with the idea that the amount of mature p53 mRNA in the nucleus controls the level of translatable p53 mRNA in heavy polysomes during induced differentiation. In our previous work we found that the induced post-transcriptional control of p53 gene expression needed a transcriptional activity. To investigate the possibility of the existence of an RNA species containing sequences homologous to a part of P 53 pre-mRNA, we used different subcloned genomic fragments as probes. Interestingly, a 3-kb HindIII fragment located at the 5' -end of the first intervening sequence of the p53 gene revealed an approximately 1.3-kb nuclear RNA, which accumulated during the induced differentiation. These observations suggest that this RNA may in some way affect the splicing of P53 pre-mRNA leading to a decrease in production of mature P53 mRNA.