Irradiation increases levels of GM-CSF through RNA stabilization which requires an AU-rich region in cancer cells.
Granulocyte/macrophage colony stimulating factor (GM-CSF) is a hematopoietic growth factor that stimulates a wide range of myeloid hematopoietic cells; RNAs coding for many oncogenes and cytokines including GM-CSF have a very short half-life. The motif of AUUUA is a highly conserved sequence in the 3'untranslated regions (3'UTR) of these transcripts and is repeated a number of times in these short-lived cytokines and oncogenes. These sequences play a major role in controlling stability of these transcripts. Human cancer cells were transfected with a chimeric rabbit beta-globin gene linked to either a 58 bp sequence of the AT-rich region from GM-CSF or a control sequence. We have found that irradiation stimulates accumulation of GM-CSF, interleukin-6 (IL-6), and IL-1 beta RNAs. In addition, this accumulation of GM-CSF was at least, in part, a result of increased stabilization of GM-CSF transcripts. Further experiments showed that irradiation increased levels of the chimeric beta-globin transcripts containing AUUUA sequences from GM-CSF, but not those containing the control sequences. Our results suggest that irradiation increases expression of GM-CSF RNA and that posttranscriptional stabilization requiring AUUUA sequences probably is in part one of the mechanisms producing the increased levels of GM-CSF RNA by irradiation.
Akashi
M
M
Division of Radiation Health, National Institute of Radiological Sciences, Chiba, Japan.
Hachiya
M
M
Koeffler
H P
HP
Suzuki
G
G
D001483:Base Sequence; D002294:Carcinoma, Squamous Cell; D015342:DNA Probes; D005822:Genetic Vectors; D005914:Globins / Q000096:biosynthesis / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009062:Mouth Neoplasms; D009838:Oligodeoxyribonucleotides; D009857:Oncogenes / Q000528:radiation effects*; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000528:radiation effects*; D014162:Transfection; D014407:Tumor Cells, Cultured
D015342:DNA Probes; D009838:Oligodeoxyribonucleotides; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005914:Globins