Global mRNA selection mechanisms for translation initiation.
Global mRNA selection mechanisms for translation initiation.
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DOI：
10.1186/s13059-014-0559-z
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发表时间：
2015-01-05
期刊：
影响因子：
12.3
通讯作者：
Ashe MP
中科院分区：
文献类型：
--
作者：
Costello J;Castelli LM;Rowe W;Kershaw CJ;Talavera D;Mohammad-Qureshi SS;Sims PF;Grant CM;Pavitt GD;Hubbard SJ;Ashe MP
从竞争的mRNA库中选择和调节单个mRNA用于翻译起始是知之甚少的过程。由eIF 4 E、eIF 4G和PABP组成的闭环复合物及其由4 E-BP进行的调节被认为是关键参与者。使用RIP-seq，我们旨在评估闭环复合物和4 E-BP在整个酵母转录组中的基因调控作用。我们发现，有不同的群体的mRNA具有连贯性的属性：一个mRNA池包含许多核糖体蛋白质的mRNA，并特别富集与所有的闭环翻译起始组件。这类可能代表严重依赖闭环复合物进行蛋白质合成的mRNA。其他大量翻译的mRNA显然在大多数闭环组分中表达不足，除了Pab 1 p。结合显示Pab 1 p相互作用和翻译水平之间密切相关的数据，这些数据表明，Pab 1 p是重要的，这些mRNA的翻译在一个闭环独立的方式。我们还确定了4 E-BP的翻译调控机制，这些似乎通过抑制自身mRNA的翻译起始进行自我调节。总的来说，我们表明，mRNA翻译起始的选择并不像以前预期的那样统一。闭环复合物的组分与许多mRNA高度相关，但一些大量翻译的mRNA与该机制的相互作用很差。因此，替代的，可能Pab 1 p依赖的机制可能存在有效地加载核糖体到mRNA上。最后，这些研究确定并表征了酵母4 E-BP的复杂自我调节回路。本文的在线版本（doi：10.1186/s13059-014-0559-z）包含补充材料，可供授权用户使用。
The selection and regulation of individual mRNAs for translation initiation from a competing pool of mRNA are poorly understood processes. The closed loop complex, comprising eIF4E, eIF4G and PABP, and its regulation by 4E-BPs are perceived to be key players. Using RIP-seq, we aimed to evaluate the role in gene regulation of the closed loop complex and 4E-BP regulation across the entire yeast transcriptome. We find that there are distinct populations of mRNAs with coherent properties: one mRNA pool contains many ribosomal protein mRNAs and is enriched specifically with all of the closed loop translation initiation components. This class likely represents mRNAs that rely heavily on the closed loop complex for protein synthesis. Other heavily translated mRNAs are apparently under-represented with most closed loop components except Pab1p. Combined with data showing a close correlation between Pab1p interaction and levels of translation, these data suggest that Pab1p is important for the translation of these mRNAs in a closed loop independent manner. We also identify a translational regulatory mechanism for the 4E-BPs; these appear to self-regulate by inhibiting translation initiation of their own mRNAs. Overall, we show that mRNA selection for translation initiation is not as uniformly regimented as previously anticipated. Components of the closed loop complex are highly relevant for many mRNAs, but some heavily translated mRNAs interact poorly with this machinery. Therefore, alternative, possibly Pab1p-dependent mechanisms likely exist to load ribosomes effectively onto mRNAs. Finally, these studies identify and characterize a complex self-regulatory circuit for the yeast 4E-BPs. The online version of this article (doi:10.1186/s13059-014-0559-z) contains supplementary material, which is available to authorized users.
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