Ribosome traffic on mRNAs maps to gene ontology: genome-wide quantification of translation initiation rates and polysome size regulation.
Ribosome traffic on mRNAs maps to gene ontology: genome-wide quantification of translation initiation rates and polysome size regulation.
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DOI：
10.1371/journal.pcbi.1002866
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发表时间：
2013
影响因子：
4.3
通讯作者：
Romano MC
中科院分区：
文献类型：
--
作者：
Ciandrini L;Stansfield I;Romano MC
为了了解管理转录丰度和编码蛋白质的水平的复杂关系，我们整合了全基因组的实验数据的核糖体密度的mRNAs与一种新的随机模型描述核糖体交通动态翻译延伸。这一分析表明，密码子排列，而不是简单的密码子偏好，在决定翻译效率的关键作用。它还表明，翻译输出是由启动效率和延长动力学。通过将全基因组实验数据集与所有酿酒酵母ORF上的核糖体交通模拟相结合，首次估计了整个转录组的mRNA特异性翻译起始速率。我们的分析确定了不同类别的mRNA，其特征在于它们的起始速率，它们的核糖体交通动力学，以及它们对核糖体可用性的反应。引人注目的是，这种基于翻译动力学的分类映射到关键的基因本体分类，揭示了翻译反应的进化优化受到基因功能的强烈影响。基因表达调控是所有生命系统的核心。在这里，我们引入了一个新的框架和方法来研究细胞中蛋白质产生的最后阶段，其中mRNA中编码的遗传信息从核苷酸的语言翻译成功能蛋白质。每个mRNA上的这一过程由几个核糖体同时进行;就像乡村小路上的汽车一样，它们不能互相超越，只能排成一队。通过将实验数据与我们模型的全基因组模拟相结合，我们分析了整个酿酒酵母基因组的核糖体流量，并首次估计了每个转录本的mRNA特异性翻译起始速率。至关重要的是，我们确定了不同类别的mRNA特征不同的核糖体交通动力学。值得注意的是，这种基于翻译动力学的分类，以及mRNA特异性起始速率的评估，映射到关键基因本体分类上，揭示了翻译反应的进化优化受到基因功能的强烈影响。
To understand the complex relationship governing transcript abundance and the level of the encoded protein, we integrate genome-wide experimental data of ribosomal density on mRNAs with a novel stochastic model describing ribosome traffic dynamics during translation elongation. This analysis reveals that codon arrangement, rather than simply codon bias, has a key role in determining translational efficiency. It also reveals that translation output is governed both by initiation efficiency and elongation dynamics. By integrating genome-wide experimental data sets with simulation of ribosome traffic on all Saccharomyces cerevisiae ORFs, mRNA-specific translation initiation rates are for the first time estimated across the entire transcriptome. Our analysis identifies different classes of mRNAs characterised by their initiation rates, their ribosome traffic dynamics, and by their response to ribosome availability. Strikingly, this classification based on translational dynamics maps onto key gene ontological classifications, revealing evolutionary optimisation of translation responses to be strongly influenced by gene function. Gene expression regulation is central to all living systems. Here we introduce a new framework and methodology to study the last stage of protein production in cells, where the genetic information encoded in the mRNAs is translated from the language of nucleotides into functional proteins. The process, on each mRNA, is carried out concurrently by several ribosomes; like cars on a small countryside road, they cannot overtake each other, and can form queues. By integrating experimental data with genome-wide simulations of our model, we analyse ribosome traffic across the entire Saccharomyces cerevisiae genome, and for the first time estimate mRNA-specific translation initiation rates for each transcript. Crucially, we identify different classes of mRNAs characterised by different ribosome traffic dynamics. Remarkably, this classification based on translational dynamics, and the evaluation of mRNA-specific initiation rates, map onto key gene ontological classifications, revealing evolutionary optimisation of translation responses to be strongly influenced by gene function.
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影响因子：
7
作者：
Beyer, A;Hollunder, J;Wilhelm, T
通讯作者：
Wilhelm, T
影响因子：
9.9
作者：
通讯作者：
--
影响因子：
4.5
作者：
Ghazalpour A;Bennett B;Petyuk VA;Orozco L;Hagopian R;Mungrue IN;Farber CR;Sinsheimer J;Kang HM;Furlotte N;Park CC;Wen PZ;Brewer H;Weitz K;Camp DG 2nd;Pan C;Yordanova R;Neuhaus I;Tilford C;Siemers N;Gargalovic P;Eskin E;Kirchgessner T;Smith DJ;Smith RD;Lusis AJ
通讯作者：
Lusis AJ
影响因子：
3.4
作者：
Chou, T
通讯作者：
Chou, T
mRNA翻译中的供求动力。
影响因子：
4.3
作者：
Brackley CA;Romano MC;Thiel M
通讯作者：
Thiel M