Rogers J T, Andriotakis J L, Lacroix L, Durmowicz G P, Kasschau K D, Bridges K R
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Nucleic Acids Res. 1994 Jul 11;22(13):2678-86. doi: 10.1093/nar/22.13.2678.
Interleukin-1 beta (Il-1 beta), a key cytokine in the acute phase response, elevates hepatic expression of both the heavy (H) and light (L) ferritin subunits without influencing the steady-state levels of either ferritin transcript. Transfection experiments with human hepatoma cells reveal that sequences within the 5' untranslated region (5'UTR) of H-ferritin mRNA confer translational regulation to chimaeric chloramphenicol acetyl transferase (CAT) mRNAs in response to Il-1 beta in the absence of marked changes in CAT mRNA levels. Il-1 beta dependent translational enhancement is mediated by a distinct G + C rich RNA sequence within 70 nucleotides (nt) of the start codon. The upstream Iron Responsive Element RNA stemloop does not confer increased expression to CAT mRNA in Il-1 beta stimulated hepatoma transfectants. A 38 nucleotide consensus sequence within the 5'UTRs of the mRNAs encoding the hepatic acute phase proteins alpha 1-antitrypsin (alpha 1AT), alpha 1-acid glycoprotein (AGP) and haptoglobin (Dente et al., 1985) is similar to sequences in the G + C rich H-ferritin mRNA translational regulatory element. Deletion of three nucleotides from this region of the 61 nt G + C rich element in the H-ferritin mRNA 5' leader eliminates Il-1 beta translational enhancement of the CAT reporter transcripts.
白细胞介素-1β（Il-1β）是急性期反应中的关键细胞因子，它可提高重链（H）和轻链（L）铁蛋白亚基的肝脏表达水平，而不影响任何一种铁蛋白转录本的稳态水平。用人肝癌细胞进行的转染实验表明，在CAT mRNA水平无明显变化的情况下，H-铁蛋白mRNA 5'非翻译区（5'UTR）内的序列可赋予嵌合氯霉素乙酰转移酶（CAT）mRNA对Il-1β的翻译调控能力。Il-1β依赖性翻译增强由起始密码子70个核苷酸（nt）内一个独特的富含G + C的RNA序列介导。上游铁反应元件RNA茎环在Il-1β刺激的肝癌转染细胞中不会使CAT mRNA的表达增加。编码肝脏急性期蛋白α1-抗胰蛋白酶（α1AT）、α1-酸性糖蛋白（AGP）和触珠蛋白的mRNA的5'UTR内一个38个核苷酸的共有序列（Dente等人，1985年）与富含G + C的H-铁蛋白mRNA翻译调控元件中的序列相似。从H-铁蛋白mRNA 5'前导序列中富含G + C的61 nt元件的该区域缺失三个核苷酸会消除Il-1β对CAT报告转录本的翻译增强作用。
