Interaction between the mRNA of the 55-kDa tumor necrosis factor receptor and cellular proteins. Possible involvement in post-transcriptional regulation of receptor expression.
Numerous effects of tumor necrosis factor are signaled by its 55-kDa receptors. Studying their expression we found that the level of receptor mRNA was decreased during the phorbol ester-induced differentiation of myelomonocytic cell lines. While only minor changes in transcription were noted, the half-life of receptor mRNA in the differentiated cells was markedly decreased, indicating the involvement of post-transcriptional regulation. In an electrophoretic mobility shift assay, formation of complexes between radiolabeled receptor mRNA and cellular proteins was observed. The decrease in receptor mRNA levels during phorbol ester-induced differentiation was paralleled by a change in the pattern of those complexes. Protein-RNA interaction was selective, as it was not competed by unrelated RNAs. Yet, certain mRNAs that contain AU-rich sequences, known to be involved in the control of their stability, did compete with the receptor mRNA, although the latter is devoid of such sequences. A region of 18 nucleotides within its coding region was found to contain an element essential for the formation of all complexes and sufficient for the formation of those with lower molecular mass. Adjacent bases were required in addition for the formation of the complexes with higher molecular mass. The results suggest that proteins interacting with this region of the 55-kDa tumor necrosis factor receptor mRNA contribute to the regulation of its expression.
Winzen
R
R
Institute of Molecular Pharmacology, Medical School, D-30623 Hannover, Federal Republic of Germany.
Kafert
S
S
Preiss
B
B
Mylius-Spencker
H A
HA
Resch
K
K
Holtmann
H
H
D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation; D006207:Half-Life; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D017931:DNA Primers; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018124:Receptors, Tumor Necrosis Factor; D013755:Tetradecanoylphorbol Acetate