Folding free energies of 5'-UTRs impact post-transcriptional regulation on a genomic scale in yeast.
Folding free energies of 5'-UTRs impact post-transcriptional regulation on a genomic scale in yeast.
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5'-UTRS的折叠自由能影响酵母基因组量表的转录后调节。
DOI：
10.1371/journal.pcbi.0010072
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发表时间：
2005-12
影响因子：
4.3
通讯作者：
Krogh M
中科院分区：
文献类型：
--
作者：
Ringnér M;Krogh M
使用高通量技术，在酿酒酵母的全基因组范围内测量了基因和蛋白质的丰度和其他特征。相比之下，仅对有限数量的基因研究了 mRNA 5'非翻译区 (UTR) 的二级结构。这里的目的是研究 mRNA 5'-UTR 折叠自由能的全基因组调控效应。我们对酿酒酵母中所有已验证基因的 5'-UTR 二级结构及其折叠自由能进行了计算。我们发现 5'-UTR 的折叠自由能与酵母全基因组研究中测量的各种转录特征之间存在显着相关性。特别是，具有弱折叠5'-UTR的mRNA具有更高的翻译率、更高的相应蛋白质丰度、更长的半衰期和更多的转录本，并且在热激后上调。此外，5'-UTR 的折叠自由能明显高于其他基因组区域和随机序列。我们还发现转录本半衰期和核糖体占用之间存在正相关性，对于短寿命转录本来说更为明显，这支持了翻译和降解之间竞争的情况。在具有强烈折叠 5'-UTR 的基因中，未表征的开放阅读框的比例过高。根据我们的分析，我们得出结论：(i) 5'-UTR 存在弱折叠的广泛偏差，(ii) 5'-UTR 的折叠自由能与基因组规模上的 mRNA 翻译和周转相关，(iii) 具有强折叠 5'-UTR 的转录本通常很少见，很难在实验中找到。在细胞中，蛋白质是由 DNA 基因复制的信使 RNA 制成的。每种蛋白质的含量需要由细胞控制。为此，细胞使用一种策略，包括分解 RNA 和改变由每种 RNA 产生的蛋白质的数量。 RNA分子的一部分称为5'非翻译区（UTR），已知该区域可以折叠成三维结构。对于某些基因来说，这样的结构对于蛋白质的产生很重要。在本文中，计算了酿酒酵母中所有基因的 5'-UTR 结构。作者表明，5'-UTR 中的结构可能在基因组中许多基因的 RNA 分解和蛋白质生产中发挥作用：具有弱折叠 5'-UTR 的 RNA 分子寿命相对较长，并产生更多蛋白质。这项研究提供了全基因组计算分析如何补充实验结果的示例。
Using high-throughput technologies, abundances and other features of genes and proteins have been measured on a genome-wide scale in Saccharomyces cerevisiae. In contrast, secondary structure in 5′–untranslated regions (UTRs) of mRNA has only been investigated for a limited number of genes. Here, the aim is to study genome-wide regulatory effects of mRNA 5′-UTR folding free energies. We performed computations of secondary structures in 5′-UTRs and their folding free energies for all verified genes in S. cerevisiae. We found significant correlations between folding free energies of 5′-UTRs and various transcript features measured in genome-wide studies of yeast. In particular, mRNAs with weakly folded 5′-UTRs have higher translation rates, higher abundances of the corresponding proteins, longer half-lives, and higher numbers of transcripts, and are upregulated after heat shock. Furthermore, 5′-UTRs have significantly higher folding free energies than other genomic regions and randomized sequences. We also found a positive correlation between transcript half-life and ribosome occupancy that is more pronounced for short-lived transcripts, which supports a picture of competition between translation and degradation. Among the genes with strongly folded 5′-UTRs, there is a huge overrepresentation of uncharacterized open reading frames. Based on our analysis, we conclude that (i) there is a widespread bias for 5′-UTRs to be weakly folded, (ii) folding free energies of 5′-UTRs are correlated with mRNA translation and turnover on a genomic scale, and (iii) transcripts with strongly folded 5′-UTRs are often rare and hard to find experimentally. In cells, proteins are made from messenger RNA copied from genes in the DNA. The amount of each protein needs to be controlled by cells. For this purpose, cells use a strategy that includes decomposing RNA and varying the number of proteins made from each RNA. One part of the RNA molecule is called the 5′–untranslated region (UTR), and it is known that this region can fold into a three-dimensional structure. For some genes, such structures are important for protein production. In this article, structures in 5′-UTRs are calculated for all genes in the yeast Saccharomyces cerevisiae. The authors show that structures in 5′-UTRs likely play a role in RNA decomposition and protein production for many genes in the genome: RNA molecules with weakly folded 5′-UTRs live relatively longer and produce more proteins. This study provides an example of how genome-wide computational analysis complements experimental results.
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影响因子：
7
作者：
Beyer, A;Hollunder, J;Wilhelm, T
通讯作者：
Wilhelm, T
DOI：
10.1083/jcb.108.2.229
发表时间：
1989-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kozak M
通讯作者：
Kozak M
影响因子：
1.8
作者：
HOFACKER, IL;FONTANA, W;SCHUSTER, P
通讯作者：
SCHUSTER, P
影响因子：
4.8
作者：
Ahmed, R;Duncan, RF
通讯作者：
Duncan, RF
影响因子：
14.9
作者：
Harris, MA;Clark, J;White, R
通讯作者：
White, R