Messenger RNA Structure Regulates Translation Initiation: A Mechanism Exploited from Bacteria to Humans.
Messenger RNA Structure Regulates Translation Initiation: A Mechanism Exploited from Bacteria to Humans.
复制标题
Messenger RNA结构调节翻译起始：从细菌到人类的一种机制。
DOI：
10.1021/acs.biochem.8b00395
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发表时间：
2018-07-03
期刊：
影响因子：
2.9
通讯作者：
Weeks KM
中科院分区：
文献类型：
--
作者：
Mustoe AM;Corley M;Laederach A;Weeks KM
RNA（mRNA）在指导这种调节中起着核心作用。mRNA转录物通过在很大程度上保持神秘的指令来调节起始过程，以实现特定的翻译效率（TE），即由给定mRNA转录物产生的蛋白质的量。TE是精确调节的，可以根据细胞类型显著变化，在不同的转录物中以数量级变化，因此构成基因表达中的重要变量。因此，了解mRNA如何编码它们自己独特的TE是生物学中的一个基本挑战。经典研究表明，mRNA可以通过折叠成促进或阻碍翻译起始的结构来编码TE。1核糖体的mRNA结合裂缝只能容纳单链mRNA。因此，翻译起始需要解折叠与起始密码子重叠的任何mRNA结构，对起始施加结构依赖性能量罚分（图1）。合成生物学家利用这些原理在很大的动态范围内调整设计的mRNA的TE，尽管有这些经典的研究，mRNA结构在调节内源基因TE中的整体重要性仍然令人惊讶地不清楚。直到最近，几乎不可能以高精度建模mRNA结构。内源性基因的研究在很大程度上依赖于计算机结构预测，只支持mRNA结构和TE之间的弱关系。这种微弱的关系究竟反映了生物学的现实，还是RNA结构建模的缺陷，一直是一个悬而未决的问题。在最近的两项研究中，2，3我们的实验室使用SHAPE-MaP RNA化学探测策略来确定数百种mRNA的高置信度，实验支持的结构模型，为重新审视这个问题提供了独特的机会。在其中一项研究中，我们使用了大约200个SHAPE-MaP确定的mRNA结构的数据集来研究简单原核生物大肠杆菌中的翻译调控。我们最初假设量化结构对TE的影响是简单的，但适当地
RNAs (mRNAs) play a central role in directing this regulation. Through instructions that remain largely cryptic, mRNA transcripts modulate the initiation process to achieve a specific translation efficiency (TE), the amount of protein made from a given mRNA transcript. TE is precisely tuned, can vary significantly depending on cell type, varies by orders of magnitude across different transcripts, and thus constitutes an essential variable in gene expression. Understanding how mRNAs encode their own unique TEs is therefore a fundamental challenge in biology. Classic studies have shown that mRNAs can encode TE by folding into structures that facilitate or impede translation initiation. 1 The mRNA-binding cleft of the ribosome can accommodate only single-stranded mRNA. Thus, translation initiation requires unfolding of any mRNA structures that overlap the start codon, imposing a structure-dependent energetic penalty on initiation (Figure 1). Synthetic biologists have harnessed these principles to tune the TEs of designed mRNAs over a large dynamic range.Despite these classic studies, the overall importance of mRNA structure in regulating TEs of endogenous genes has remained surprisingly unclear. Until recently, it has been all but impossible to model mRNA structure with high accuracy. Studies of endogenous genes have largely relied on in silico structure predictions that have supported only a weak relationship between mRNA structure and TE. Whether this weak relationship reflected biological reality or the shortcomings of RNA structure modeling was a persistent unanswered question. In two recent studies, 2, 3 our laboratories used the SHAPE-MaP RNA chemical probing strategy to determine high-confidence, experimentally supported structure models for hundreds of mRNAs, providing a unique opportunity to revisit this question. In one of these studies, 2 we used a data set of approximately 200 SHAPE-MaP-determined mRNA structures to investigate translation regulation in the simple prokaryote Escherichia coli. We initially assumed that it would be straightforward to quantify the influence of structure on TE, but properly
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影响因子：
5.6
作者：
de Smit, MH;van Duin, J
通讯作者：
van Duin, J
DOI：
10.1073/pnas.1706539114
发表时间：
2017-11-21
影响因子：
11.1
作者：
Corley M;Solem A;Phillips G;Lackey L;Ziehr B;Vincent HA;Mustoe AM;Ramos SBV;Weeks KM;Moorman NJ;Laederach A
通讯作者：
Laederach A
影响因子：
64.5
作者：
Mustoe AM;Busan S;Rice GM;Hajdin CE;Peterson BK;Ruda VM;Kubica N;Nutiu R;Baryza JL;Weeks KM
通讯作者：
Weeks KM
影响因子：
46.9
作者：
Liang, Xue-hai;Shen, Wen;Crooke, Stanley T.
通讯作者：
Crooke, Stanley T.