POSITION IS THE CRITICAL DETERMINANT FOR FUNCTION OF IRON-RESPONSIVE ELEMENTS AS TRANSLATIONAL REGULATORS
POSITION IS THE CRITICAL DETERMINANT FOR FUNCTION OF IRON-RESPONSIVE ELEMENTS AS TRANSLATIONAL REGULATORS
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DOI：
10.1128/mcb.12.5.1959
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发表时间：
1992-05-01
影响因子：
5.3
通讯作者：
HENTZE, MW
中科院分区：
文献类型：
--
作者：
GOOSSEN, B;HENTZE, MW
至少两组真核 mRNA（铁蛋白和红系 5-氨基乙酰丙酸合酶）通过位于其 mRNA 5' 非翻译区内保守位置的铁响应元件 (IRE) 进行翻译调节。我们确定 mRNA 5' 末端和 IRE 之间的间距决定了 IRE 介导铁依赖性翻译抑制的潜力。 RNA 间隔区的长度而不是其核苷酸序列或预测的二级结构被证明是 IRE 功能的主要决定因素。当保留 IRE 的位置时，天然铁蛋白 mRNA 中 IRE 侧翼的序列可以被改变的侧翼序列替换，而不影响体内 IRE 的调节功能。这些结果将位置定义为体内 IRE 功能的关键顺式要求，并意味着利用转录起始位点选择来调节该翻译调节因子的功能的潜力。
At least two groups of eukaryotic mRNAs (ferritin and erythroid 5-aminolevulinate synthase) are translationally regulated via iron-responsive elements (IREs) located in a conserved position within the 5' untranslated regions of their mRNAs. We establish that the spacing between the 5' terminus of an mRNA and the IRE determines the potential of the IRE to mediate iron-dependent translational repression. The length of the RNA spacer rather than its nucleotide sequence or predicted secondary structure is shown to be the primary determinant of IRE function. When the position of the IRE is preserved, sequences flanking the IRE in natural ferritin mRNA can be replaced by altered flanking sequences without affecting the regulatory function of the IRE in vivo. These results define position as a critical cis requirement for IRE function in vivo and imply the potential to utilize transcription start site selection to modulate the function of this translational regulator.