During embryogenesis, Hox mRNA translation is tightly regulated by a sophisticated molecular mechanism that combines two RNA regulons located in their 5′UTR. First, an Internal Ribosome Entry Site (IRES) enables cap-independent translation. Second, a Translation Inhibitory Element or TIE, which ensures concomitant cap-dependent translation inhibition. Here, we deciphered the molecular mechanisms of Hox a3 and a11 TIE elements. Both TIEs possess an upstream Open Reading Frame (uORF) that is critical to inhibit cap-dependent translation but with different mechanisms. In TIE a3, we identify a uORF which inhibits cap-dependent translation and requires the non-canonical initiation factor eIF2D. TIE a11 also contains a uORF but it is a minimal uORF formed by an uAUG followed immediately by a stop codon, namely a 'start-stop'. The a11 'start-stop' sequence is located upstream of a highly stable stem loop structure which stalls the 80S ribosome and thereby inhibits cap-dependent translation of Hox a11 main ORF.

中文翻译：

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Hox a3和a11 mRNA的翻译抑制元件使用uORF抑制翻译

在胚胎发生过程中，Hox mRNA的翻译受到复杂的分子机制的严格调控，该机制结合了位于其5'UTR中的两个RNA调节子。首先，内部核糖体进入位点（IRES）可以进行不依赖帽的翻译。第二，翻译抑制元件或TIE，其确保相应的帽依赖性翻译抑制。在这里，我们破译了Hox a3和a11 TIE元素的分子机制。这两个TIE均具有上游开放阅读框（uORF），这对于抑制依赖于帽的翻译至关重要，但机制不同。在TIE a3中，我们确定了一个uORF，它可以抑制依赖于帽的翻译，并且需要非典型的起始因子eIF2D。TIE a11也包含一个uORF，但它是一个由uAUG紧随其后的终止密码子（即“起始-终止”）形成的最小uORF。A11'