Community effects in regulation of translation.
Community effects in regulation of translation.
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DOI：
10.7554/elife.10965
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发表时间：
2016-04-22
期刊：
影响因子：
7.7
通讯作者：
Kenny A
中科院分区：
文献类型：
--
作者：
Macdonald PM;Kanke M;Kenny A
某些形式的翻译调控以及翻译本身依赖于与 mRNA 不同末端结合的蛋白质之间的长程相互作用。一个普遍的假设是，这种相互作用仅发生在顺式，即单个转录本的两端之间。然而，果蝇 oskar (osk) mRNA 的某些翻译调控缺陷可以通过反式修复。我们提出，通过颗粒中 mRNA 的组装促进转录间相互作用，使调控元件能够反式发挥作用。在这里，我们证实了该模型的预测，并表明 PTB 依赖性粒子组装的破坏会抑制反式救援。转录本之间的通讯不限于不同的 osk mRNA，因为嵌入 osk mRNA 中的顺式作用元件施加的调节会传播到 gurken mRNA。我们得出的结论是，翻译调控中存在社区效应。 DOI：http://dx.doi.org/10.7554/eLife.10965.001 基因编码制造蛋白质和其他分子所需的指令。为了制造蛋白质，基因内的 DNA 被复制以产生信使核糖核酸 (mRNA) 分子，然后将其用作模板，通过称为翻译的过程构建蛋白质。这个过程涉及被称为核糖体的蛋白质机器与 mRNA 起始端的结合，受到严格调控，以控制细胞中特定蛋白质的数量。例如，在果蝇卵巢中，一种名为 Bruno 的蛋白质既抑制又激活一种名为 oskar 的基因的翻译。为了实现这一目标，Bruno 与 oskar RNA 末端附近的区域（称为 Bruno 响应元件）结合。目前尚不清楚布鲁诺如何控制翻译。然而，由于核糖体在 mRNA 起始处附近开始翻译，而 Bruno 结合在 mRNA 末端附近的区域，因此 mRNA 两端之间必定存在长程相互作用。通常认为这种长程相互作用仅发生在与同一 mRNA 分子结合的蛋白质之间。然而，2010 年，研究人员观察到，一种 oskar mRNA 中的 Bruno 反应元件可能会影响其他 oskar mRNA 的翻译。这被称为“反式监管”。在这里，麦克唐纳等人。 – 包括早期工作中的一些研究人员 – 在果蝇中更详细地研究了这一观察结果。在细胞中，多个 mRNA 分子及其相关蛋白可以组装成颗粒。麦克唐纳等人。提出这些颗粒中许多 mRNA 分子的紧密接近可能会导致反式调节的发生。事实上，实验发现，阻断 oskar mRNA 组装成颗粒可以抑制反式调节，正如预期的那样。麦克唐纳等人。还询问编码不同蛋白质的 mRNA 之间是否可以发生反式调节。实验表明，即使 oskar mRNA 没有被翻译，oskar mRNA 也可以阻断 gurken 基因产生的 mRNA 的翻译。需要做更多的工作来找出反式调控在控制翻译方面的应用范围。 DOI：http://dx.doi.org/10.7554/eLife.10965.002
Certain forms of translational regulation, and translation itself, rely on long-range interactions between proteins bound to the different ends of mRNAs. A widespread assumption is that such interactions occur only in cis, between the two ends of a single transcript. However, certain translational regulatory defects of the Drosophila oskar (osk) mRNA can be rescued in trans. We proposed that inter-transcript interactions, promoted by assembly of the mRNAs in particles, allow regulatory elements to act in trans. Here we confirm predictions of that model and show that disruption of PTB-dependent particle assembly inhibits rescue in trans. Communication between transcripts is not limited to different osk mRNAs, as regulation imposed by cis-acting elements embedded in the osk mRNA spreads to gurken mRNA. We conclude that community effects exist in translational regulation. DOI: http://dx.doi.org/10.7554/eLife.10965.001 Genes encode the instructions needed to make proteins and other molecules. To make a protein, the DNA within a gene is copied to produce molecules of messenger ribonucleic acid (mRNA) that are then used as templates to build proteins via a process called translation. This process – which involves protein machines called ribosomes binding to the start of the mRNA – is tightly regulated to control the amounts of particular proteins in cells. For example, in fruit fly ovaries, a protein called Bruno both represses and activates the translation of a gene known as oskar. To achieve this, Bruno binds to regions near the end of the oskar RNA known as Bruno response elements. It is not clear how Bruno acts to control translation. However, because ribosomes begin translation near the start of the mRNA, while Bruno is bound to regions near the end of the mRNA, there must be long-range interactions between the two ends of the mRNA. It is generally assumed that such long-range interactions only occur between proteins that are bound to the same mRNA molecule. However, in 2010, researchers observed that Bruno response elements within one oskar mRNA could influence the translation of other oskar mRNAs. This is known as “regulation in trans”. Here, Macdonald et al. – including some of the researchers from the earlier work – investigated this observation in more detail in fruit flies. In cells, multiple mRNA molecules and their associated proteins can assemble into particles. Macdonald et al. proposed that the close proximity of many mRNA molecules in these particles could allow trans regulation to take place. Indeed, the experiments found that blocking the assembly of oskar mRNA into particles inhibited trans regulation as expected. Macdonald et al. also asked if trans regulation can occur between mRNAs that encode different proteins. The experiments show that oskar mRNA could block the translation of an mRNA produced by the gurken gene, even when oskar mRNA was not being translated. More work is needed to find out how widely trans regulation is used to control translation. DOI: http://dx.doi.org/10.7554/eLife.10965.002