Rps26 directs mRNA-specific translation by recognition of Kozak sequence elements.

Rps26 directs mRNA-specific translation by recognition of Kozak sequence elements.
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RPS26通过识别Kozak序列元件来指导mRNA特异性翻译。

DOI:
10.1038/nsmb.3442
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发表时间:
2017-09
影响因子:
16.8
通讯作者:
Karbstein K
Karbstein K
中科院分区:
生物学1区
文献类型:
--
作者:
Ferretti MB;Ghalei H;Ward EA;Potts EL;Karbstein K

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我们描述了一种新的方法,从相同的细胞中分离两个核糖体群体,并使用这种方法和RNA-seq来鉴定与S结合的mRNA。有和没有Rps 26的酿酒核糖体,Rps 26是一种与戴蒙德·布莱克凡贫血(DBA)发病机制相关的蛋白质。这些分析表明,Rps 26有助于mRNA特异性翻译的Kozak序列的识别良好翻译的mRNA,Rps 26缺陷的核糖体优先翻译mRNA从选择的压力反应途径。令人惊讶的是,酵母暴露于这些压力导致Rps 26缺陷型核糖体的形成和其靶mRNA的翻译增加。这些结果描述了一个新的范例,生产专门的核糖体,发挥生理作用,在增强的良好特征的转录应激反应与迄今为止未知的翻译反应,从而创建一个前馈环基因表达。此外,Rps 26缺陷核糖体同时出现的功能获得和功能丧失表型可以解释DBA的发病机制。
We describe a novel approach to separate two ribosome populations from the same cells and use this method, and RNA-seq, to identify the mRNAs bound to S. cerevisiae ribosomes with and without Rps26, a protein linked to the pathogenesis of Diamond Blackfan Anemia (DBA). These analyses reveal that Rps26 contributes to mRNA-specific translation by recognition of the Kozak sequence in well-translated mRNAs, and that Rps26-deficient ribosomes preferentially translate mRNA from select stress response pathways. Surprisingly, exposure of yeast to these stresses leads to the formation of Rps26-deficient ribosomes and to the increased translation of their target mRNAs. These results describe a novel paradigm, the production of specialized ribosomes, which play physiological roles in augmenting the well-characterized transcriptional stress response with a heretofore unknown translational response, thereby creating a feed forward loop in gene-expression. Moreover, the simultaneous gain-of-function and loss-of-function phenotypes from Rps26-deficient ribosomes can explain the pathogenesis of DBA.
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