An antisense RNA involved in p53 mRNA maturation in murine erythroleukemia cells induced to differentiate.

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RESUMO

A post-transcriptional control of gene expression was found to be responsible for a down-regulation of p53 mRNA accompanying the induced differentiation of murine erythroleukemia (MEL) cells. Such a post-transcriptional control was governed by the induced synthesis of an RNA species (inRNA). In an attempt to find a potential candidate for such a function, we have localized the post-transcriptional regulation of p53 mRNA in the nuclear compartment of the cells; the various fragments of the p53 gene were used as probes for induced RNA(s) susceptible to interacting with p53 pre-mRNA. This experimental approach allowed for the identification of a nuclear RNA molecule, approximately 1.3 kb long, which was recognized specifically by a PstI-HindIII fragment located in the 5' part of the first intervening sequence of the p53 gene. This RNA accumulated when cell were treated by the inducer concomitantly with high mol.wt p53 mRNA precursors. However this RNA was not a maturation product of p53 pre-mRNA as evidenced by its antisense orientation with respect to this RNA. Moreover it was markedly enriched in the poly(A)+ fraction. The complementary part of inRNA in the p53 gene has been sequenced over approximately 1200 bp; no extensive homology was found in gene data banks but three restricted areas of the sequence were found homologous to a limited number of genes; they were themselves partially homologous to known repetitive sequences. Possible implication of such a sequence in the regulation of p53 gene expression is discussed.

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