Akashi M, Hachiya M, Koeffler H P, Suzuki G
Division of Radiation Health, National Institute of Radiological Sciences, Chiba, Japan.
Biochem Biophys Res Commun. 1992 Dec 15;189(2):986-93. doi: 10.1016/0006-291x(92)92301-d.
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.
粒细胞/巨噬细胞集落刺激因子（GM-CSF）是一种造血生长因子，可刺激多种髓系造血细胞；编码包括GM-CSF在内的许多癌基因和细胞因子的RNA半衰期非常短。AUUUA基序是这些转录本3'非翻译区（3'UTR）中高度保守的序列，在这些短寿命的细胞因子和癌基因中重复多次。这些序列在控制这些转录本的稳定性方面起主要作用。用人癌细胞转染与GM-CSF富含AT区域的58 bp序列或对照序列相连的嵌合兔β-珠蛋白基因。我们发现辐射刺激GM-CSF、白细胞介素-6（IL-6）和IL-1βRNA的积累。此外，GM-CSF的这种积累至少部分是GM-CSF转录本稳定性增加的结果。进一步的实验表明，辐射增加了含有GM-CSF的AUUUA序列的嵌合β-珠蛋白转录本的水平，但不增加含有对照序列的转录本的水平。我们的结果表明，辐射增加了GM-CSF RNA的表达，并且需要AUUUA序列的转录后稳定可能部分是辐射产生GM-CSF RNA水平增加的机制之一。
