Upstream sequence elements direct post-transcriptional regulation of gene expression under stress conditions in yeast.
Upstream sequence elements direct post-transcriptional regulation of gene expression under stress conditions in yeast.
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DOI：
10.1186/1471-2164-10-7
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发表时间：
2009-01-07
期刊：
影响因子：
4.4
通讯作者：
Hubbard SJ
中科院分区：
文献类型：
--
作者：
Lawless C;Pearson RD;Selley JN;Smirnova JB;Grant CM;Ashe MP;Pavitt GD;Hubbard SJ
真核细胞中基因表达的控制发生在转录和转录后。虽然现在已知许多基因在翻译水平上受到调控，但一般而言，其机制知之甚少。我们以前提出了多聚体梯度和阵列为基础的证据，翻译控制是广泛的，在相当数量的基因，当酵母细胞暴露于一系列的压力。在这里，我们重新检查了这些基因集，考虑到UTR序列在这些基因的翻译反应中的作用，使用最近的大规模数据集，定义了许多酵母基因的5'和3'转录末端。特别是，我们强调了5'UTR和上游开放阅读框架（uORF）的潜在作用。我们显示了在特定GO功能类别中对于在给定应激下被过度上调和下调的基因的高度显著的富集（例如，碳水化合物代谢在氨基酸饥饿下被上调）。将这些数据与应激反应数据交叉参考，我们表明，转录上调的基因具有较长的5'UTR，这与它们在翻译调控中的作用一致。在第一个全基因组的研究uORF在一组映射的5'UTR，我们表明，uORF是罕见的，是统计学上的UTR序列中的代表。然而，它们具有与它们在翻译控制中的假定作用一致的独特的组成偏差，并且在明显上调的基因中更常见。这些结果证明了UTR序列，特别是5'UTR的中心调节作用，突出了uORF在酵母中转录后控制中的重要作用。酵母uORF比已经提出的更高度保守，进一步强调了它们作为参与基因调控的功能元件的重要性。它还表明了一种更复杂和新的控制机制，即uORF允许基因在应激条件下逃避更普遍的翻译衰减。然而，由于uORF相对罕见（只有约13%的酵母基因具有它们），关于UTR元件如何在胁迫下指导数百个基因的翻译控制，仍然存在许多未回答的问题。
The control of gene expression in eukaryotic cells occurs both transcriptionally and post-transcriptionally. Although many genes are now known to be regulated at the translational level, in general, the mechanisms are poorly understood. We have previously presented polysomal gradient and array-based evidence that translational control is widespread in a significant number of genes when yeast cells are exposed to a range of stresses. Here we have re-examined these gene sets, considering the role of UTR sequences in the translational responses of these genes using recent large-scale datasets which define 5' and 3' transcriptional ends for many yeast genes. In particular, we highlight the potential role of 5' UTRs and upstream open reading frames (uORFs). We show a highly significant enrichment in specific GO functional classes for genes that are translationally up- and down-regulated under given stresses (e.g. carbohydrate metabolism is up-regulated under amino acid starvation). Cross-referencing these data with the stress response data we show that translationally upregulated genes have longer 5' UTRs, consistent with their role in translational regulation. In the first genome-wide study of uORFs in a set of mapped 5' UTRs, we show that uORFs are rare, being statistically under-represented in UTR sequences. However, they have distinct compositional biases consistent with their putative role in translational control and are more common in genes which are apparently translationally up-regulated. These results demonstrate a central regulatory role for UTR sequences, and 5' UTRs in particular, highlighting the significant role of uORFs in post-transcriptional control in yeast. Yeast uORFs are more highly conserved than has been suggested, lending further weight to their significance as functional elements involved in gene regulation. It also suggests a more complex and novel mechanism of control, whereby uORFs permit genes to escape from a more general attenuation of translation under conditions of stress. However, since uORFs are relatively rare (only ~13% of yeast genes have them) there remain many unanswered questions as to how UTR elements can direct translational control of many hundreds of genes under stress.
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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：
30.8
作者：
Man, Orna;Pilpel, Yitzhak
通讯作者：
Pilpel, Yitzhak
影响因子：
5.3
作者：
GRANT, CM;HINNEBUSCH, AG
通讯作者：
HINNEBUSCH, AG
影响因子：
5.8
作者：
Bonnet, E;Wuyts, J;Van de Peer, Y
通讯作者：
Van de Peer, Y
使用启发式和进化保护鉴定酵母基因组中推定的调节性上游ORF。
影响因子：
3
作者：
通讯作者：
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