Connecting variability in global transcription rate to mitochondrial variability.
Connecting variability in global transcription rate to mitochondrial variability.
复制标题
DOI：
10.1371/journal.pbio.1000560
复制
发表时间：
2010-12-14
期刊：
影响因子：
9.8
通讯作者：
Iborra FJ
中科院分区：
文献类型：
--
作者：
das Neves RP;Jones NS;Andreu L;Gupta R;Enver T;Iborra FJ
作者证明了转录速率的可变性和细胞线粒体含量的差异之间的联系。基因相同的真核细胞群体在基因表达上表现出显著的细胞间差异。然而，我们对这种变异的起源缺乏很好的理解。我们发现平均细胞转录速率在细胞间存在显著的可变性。我们还发现，细胞线粒体质量的数量在细胞间存在显著的变异性。我们进行了融合研究，表明转录速率的可变性取决于小的扩散因子。此后，体外研究表明，转录速率对[ATP]有敏感的依赖关系，但与其他核苷酸三磷酸(NTPs)的浓度无关。通过改变营养水平和可利用的[ATP]来扰乱人群的进一步实验表明，这种联系在体内是成立的。我们发现有证据表明，线粒体质量或总膜电位越高的细胞，单位体积核物质的转录速度越快。我们还发现证据表明，转录速率的可变性在很大程度上受到抗氧化剂或促氧化剂的影响。子代研究表明，线粒体含量变化的一个原因显然是线粒体在分裂时的随机分离。我们最后注意到，随机遗传的线粒体质量低于姐妹的女儿拥有相对较长的细胞周期。我们的发现揭示了能量代谢的可变性和转录速率的可变性之间的联系。尽管成对的细胞可能有相同的基因，但它们仍然表现出行为上的差异。这些细胞间的差异可能是由于细胞机制转录和翻译基因的方式不同造成的。识别这种变异的起源很重要，因为它有助于我们理解为什么基因相同的细胞可以对环境做出一系列反应。在这项工作中，我们测量了这些基因在培养的人类细胞中产生转录本的速度。我们发现平均转录速率在细胞间存在显著的可变性。这种可变性与线粒体含量有关。线粒体质量较高的细胞转录速度较快，我们表明这种差异性的部分原因是当细胞分裂时，线粒体对子细胞的分配不均匀。此外，我们发现继承更多线粒体的细胞分裂得更早。这些发现在转录产物的可变性和细胞线粒体内容的可变性之间建立了联系。
The authors demonstrate a connection between variability in the rate of transcription and differences in cellular mitochondrial content. Populations of genetically identical eukaryotic cells show significant cell-to-cell variability in gene expression. However, we lack a good understanding of the origins of this variation. We have found marked cell-to-cell variability in average cellular rates of transcription. We also found marked cell-to-cell variability in the amount of cellular mitochondrial mass. We undertook fusion studies that suggested that variability in transcription rate depends on small diffusible factors. Following this, in vitro studies showed that transcription rate has a sensitive dependence on [ATP] but not on the concentration of other nucleotide triphosphates (NTPs). Further experiments that perturbed populations by changing nutrient levels and available [ATP] suggested this connection holds in vivo. We found evidence that cells with higher mitochondrial mass, or higher total membrane potential, have a faster rate of transcription per unit volume of nuclear material. We also found evidence that transcription rate variability is substantially modulated by the presence of anti- or prooxidants. Daughter studies showed that a cause of variability in mitochondrial content is apparently stochastic segregation of mitochondria at division. We conclude by noting that daughters that stochastically inherit a lower mitochondrial mass than their sisters have relatively longer cell cycles. Our findings reveal a link between variability in energy metabolism and variability in transcription rate. Though pairs of cells may have identical genes, they still show behavioural differences. These cell-to-cell differences may arise from variations in how genes are transcribed and translated by the cellular machinery. Identifying the origins of this variation is important as it helps us understand why genetically identical cells can show a range of responses to the environment. In this work, we measured the rate at which the genes yield transcripts in cultured human cells. We found marked cell-to-cell variability in average rates of transcription. This variability is related to mitochondrial content. Cells with a higher mitochondrial mass have a faster rate of transcription, and we show that part of this variability is due to the unequal distribution of mitochondria to daughter cells when cells divide. Additionally, we find that cells that inherit more mitochondria divide earlier. These findings make a connection between variability in transcript production and variability in cellular mitochondrial content.
登录
查看更多内容
DOI：
10.1083/jcb.153.7.1341
发表时间：
2001-06-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kimura H;Cook PR
通讯作者：
Cook PR
活细胞中 RNA 聚合酶 II 的转录周期。
影响因子：
7.8
作者：
Kimura, Hiroshi;Sugaya, Kimihiko;Cook, Peter R
通讯作者：
Cook, Peter R
影响因子：
2.3
作者：
Iborra, FJ
通讯作者：
Iborra, FJ
影响因子：
56.9
作者：
Dennis, PB;Jaeschke, A;Thomas, G
通讯作者：
Thomas, G
影响因子：
2.3
作者：
Iborra, Francisco J.;Buckle, Veronica
通讯作者：
Buckle, Veronica