Translational Control via Protein-Regulated Upstream Open Reading Frames
Translational Control via Protein-Regulated Upstream Open Reading Frames
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DOI：
10.1016/j.cell.2011.05.005
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发表时间：
2011-06-10
期刊：
影响因子：
64.5
通讯作者：
Hentze, Matthias W.
中科院分区：
文献类型：
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作者：
Medenbach, Jan;Seiler, Markus;Hentze, Matthias W.
性致死性（Sex lethal， SXL）对msl-2 mRNA的调控是果蝇剂量补偿的关键，分析发现了一种基于常见的50个非翻译区元件、上游开放阅读框（open reading frame, uorf）和rna结合蛋白相互作用位点的翻译控制模式。研究表明，短uORF下游的SXL结合对主读框翻译产生强烈的负面影响。潜在的机制包括增加扫描核糖体在uORF的起始和增加其对下游翻译的障碍。我们的分析表明，SXL在uORF上起作用，而不是控制延伸或终止。探究潜在机制的普遍性，我们发现我们在实验中定义的调节模块在异源环境中起作用，并且我们确定了通过该模块调节的天然果蝇mrna。我们认为蛋白质调控的uORFs构成了调节蛋白质合成的系统原理。
Analysis of the regulation of msl-2 mRNA by Sex lethal (SXL), which is critical for dosage compensation in Drosophila, has uncovered a mode of translational control based on common 50 untranslated region elements, upstream open reading frames (uORFs), and interaction sites for RNA-binding proteins. We show that SXL binding downstream of a short uORF imposes a strong negative effect on major reading frame translation. The underlying mechanism involves increasing initiation of scanning ribosomes at the uORF and augmenting its impediment to downstreamtranslation. Our analyses reveal that SXL exerts its effect controlling initiation, not elongation or termination, at the uORF. Probing the generality of the underlying mechanism, we show that the regulatorymodule that we define experimentally functions in a heterologous context, and we identify natural Drosophila mRNAs that are regulated via this module. We propose that protein-regulated uORFs constitute a systematic principle for the regulation of protein synthesis.