Conserved translatome remodeling in nematode species executing a shared developmental transition.

Conserved translatome remodeling in nematode species executing a shared developmental transition.
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DOI:
10.1371/journal.pgen.1003739
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发表时间:
2013
期刊:
影响因子:
4.5
通讯作者:
Fire A
Fire A
中科院分区:
生物学2区
文献类型:
--
作者:
Stadler M;Fire A

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线虫属线虫在缺乏食物的情况下孵化后进入发育滞育状态。为了更好地了解不同调控方式对与这种发育转变相关的基因表达变化的相对贡献,我们使用核糖体图谱和mRNA-SEQ表征了与L1滞育退出相关的全基因组范围的mRNA丰度和翻译效率的变化。我们发现翻译调控和mRNA丰度过程有协同作用的强烈趋势,共同影响基因表达程序的戏剧性重塑。虽然观察到了物种之间的基因特异性差异,但总体翻译动力学在广泛和功能上是保守的。反应的一个显著的、保守的特征是在L1滞育期间核糖体蛋白的强烈翻译抑制,随后在恢复发育时激活。在全球范围内,核糖体足迹丰度的变化比mRNA丰度的变化显示出物种之间更大的相似性,这表明翻译调控对进化维持稳定的基因表达做出了实质性的和全基因组的贡献。与一组四个相关的动物物种合作,我们在蛋白质生产和RNA水平调节的水平上研究了保守的发育和代谢转变。值得注意的是,RNA积累和蛋白质合成水平上的调控效应共同作用,实现了观察到的代谢转变。除了个体基因调控的基本基础总体上保持不变外,这两个过程--信使核糖核酸的产生和蛋白质合成--的改变可以在进化过程中相互补充,以维持稳定数量的功能基因产物。观察到的调控的一个显著特征是在代谢停滞(滞育)期间存储编码蛋白质合成机制关键成员的空闲mRNAs。维持这一池有助于在摄食后重新激活,蛋白质合成能力的快速再生是适应重大代谢转变的早期和关键功能。
Nematodes of the genus Caenorhabditis enter a developmental diapause state after hatching in the absence of food. To better understand the relative contributions of distinct regulatory modalities to gene expression changes associated with this developmental transition, we characterized genome-wide changes in mRNA abundance and translational efficiency associated with L1 diapause exit in four species using ribosome profiling and mRNA-seq. We found a strong tendency for translational regulation and mRNA abundance processes to act synergistically, together effecting a dramatic remodeling of the gene expression program. While gene-specific differences were observed between species, overall translational dynamics were broadly and functionally conserved. A striking, conserved feature of the response was strong translational suppression of ribosomal protein production during L1 diapause, followed by activation upon resumed development. On a global scale, ribosome footprint abundance changes showed greater similarity between species than changes in mRNA abundance, illustrating a substantial and genome-wide contribution of translational regulation to evolutionary maintenance of stable gene expression. Working with a set of four related animal species, we have studied a conserved developmental and metabolic transition at the level of protein production and regulation of RNA levels. Strikingly, regulatory effects at the level of RNA accumulation and protein synthesis act together to achieve the observed metabolic shift. In addition to a general conservation of the underlying basis for the regulation of individual genes, alterations of these two processes—mRNA production and protein synthesis—can compensate for one another during evolution to maintain stable amounts of functional gene products. A salient feature of the observed regulation was the storage of idle mRNAs encoding key members of the protein synthesis machinery during metabolic arrest (diapause). Maintenance of this pool facilitates re-activation upon feeding, with the rapid regeneration of protein synthesis capacity an early and critical function during adaptation to a major metabolic shift.
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影响因子: 11.1
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