INTERACTION BETWEEN THE MESSENGER-RNA OF THE 55-KDA TUMOR-NECROSIS-FACTOR RECEPTOR AND CELLULAR PROTEINS - POSSIBLE INVOLVEMENT IN POSTTRANSCRIPTIONAL REGULATION OF RECEPTOR EXPRESSION

Numerous effects of tumor necrosis factor are signaled by its 55-kDa r eceptors, Studying their expression we found that the level of recepto r mRNA was decreased during the phorbol ester-induced differentiation of myelomonocytic cell lines, While only minor changes in transcriptio n were noted, the half-life of receptor mRNA in the differentiated cel ls was markedly decreased, indicating the involvement of post transcri ptional regulation, In an electrophoretic mobility shift assay, format ion of complexes between radiolabeled receptor mRNA and cellular prote ins was observed, The decrease in receptor mRNA levels during phorbol ester-induced differentiation was paralleled by a change in the patter n of those complexes, Protein-RNA interaction was selective, as it was not competed by unrelated RNAs, Yet, certain mRNAs that contain AU-ri ch sequences, known to be involved in the control of their stability, did compete with the receptor mRNA, although the latter is devoid of s uch sequences, A region of 18 nucleotides within its coding region was found to contain an element essential for the formation of all comple xes and sufficient for the formation of those with lower molecular mas s, Adjacent bases were required in addition for the formation of the c omplexes with higher molecular mass, The results suggest that proteins interacting with this region of the 55-kDa tumor necrosis factor rece ptor mRNA contribute to the regulation of its expression.