Quantifying negative feedback regulation by micro-RNAs.

Quantifying negative feedback regulation by micro-RNAs.
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DOI:
10.1088/1478-3975/8/5/055002
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发表时间:
2011-10
期刊:
影响因子:
2
通讯作者:
Raghavachari S
Raghavachari S
中科院分区:
生物学4区
文献类型:
--
作者:
Wang S;Raghavachari S

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micro-RNAs(miRNAs)通过与靶mRNA配对抑制蛋白质的产生,在转录后基因调控中发挥重要作用。研究表明,超过三分之一的人类基因被miRNA靶向。尽管已经在哺乳动物基因组中鉴定了数百种miRNA,但在基因调控网络的背景下,基于miRNA的抑制的功能仍然不清楚。在这项研究中,我们探讨了反馈调节的功能作用的miRNAs。在一个模型中,翻译的抑制通过miRNA螯合mRNA发生,我们发现miRNA和mRNA水平是反相关的,导致蛋白质水平的波动比理论上预期的更大,假设miRNA和mRNA水平之间没有相关性。如果miRNA抑制是由于翻译速率的催化抑制,我们分析表明,蛋白质的波动可以强烈抑制miRNA的调控。我们还讨论了这些模式中的任何一种可能与细胞功能有关。
Micro-RNAs (miRNAs) play a crucial role in post-transcriptional gene regulation by pairing with target mRNAs to repress protein production. It has been shown that over one-third of human genes are targeted by miRNA. Although hundreds of miRNAs have been identified in mammalian genomes, the function of miRNA-based repression in the context of gene regulation networks still remains unclear. In this study, we explore the functional roles of feedback regulation by miRNAs. In a model where repression of translation occurs by sequestration of mRNA by miRNA, we find that miRNA and mRNA levels are anti-correlated, resulting in larger fluctuation in protein levels than theoretically expected assuming no correlation between miRNA and mRNA levels. If miRNA repression is due to a catalytic suppression of translation rates, we analytically show that the protein fluctuations can be strongly repressed with miRNA regulation. We also discuss how either of these modes may be relevant for cell function.
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