mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues.
mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues.
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DOI：
10.1016/j.molcel.2014.08.028
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发表时间：
2014-10-02
期刊：
影响因子：
16
通讯作者：
Bartel, David P.
中科院分区：
文献类型：
--
作者：
Eichhorn, Stephen W.;Guo, Huili;McGeary, Sean E.;Rodriguez-Mias, Ricard A.;Shin, Chanseok;Baek, Daehyun;Hsu, Shu-hao;Ghoshal, Kalpana;Villen, Judit;Bartel, David P.
MicroRNAs （miRNAs）通过翻译抑制和mRNA不稳定的结合来调节靶mRNA，在全球研究的少数情况下，mRNA不稳定在稳态下占主导地位。在这里，我们将全局稳态测量扩展到其他哺乳动物环境，并发现无论miRNA，细胞类型，生长条件或翻译状态如何，mRNA不稳定解释了大多数（66%至90%）miRNA介导的抑制。我们还确定了当miRNA被诱导时，内源性mRNA的翻译抑制和mRNA不稳定的相对动力学。虽然翻译抑制发生迅速，但其影响相对较弱，因此当相应的抑制随之而来时，mRNA不稳定的影响占主导地位。这些结果表明，由此产生的mirna介导的抑制在很大程度上是不可逆的，并为mirna介导的调控性质提供了其他见解。它们还简化了未来的研究，极大地扩展了监测mRNA变化捕获大多数直接miRNA效应的已知背景和时间点。
MicroRNAs (miRNAs) regulate target mRNAs through a combination of translational repression and mRNA destabilization, with mRNA destabilization dominating at steady state in the few contexts examined globally. Here, we extend the global steady-state measurements to additional mammalian contexts and find that regardless of the miRNA, cell type, growth condition, or translational state, mRNA destabilization explains most (66% to >90%) miRNA-mediated repression. We also determine the relative dynamics of translational repression and mRNA destabilization for endogenous mRNAs as a miRNA is induced. Although translational repression occurs rapidly, its effect is relatively weak, such that by the time consequential repression ensues, the effect of mRNA destabilization dominates. These results imply that consequential miRNA-mediated repression is largely irreversible and provide other insights into the nature of miRNA-mediated regulation. They also simplify future studies, dramatically extending the known contexts and time points for which monitoring mRNA changes captures most of the direct miRNA effects.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
DOI：
10.1126/science.1215691
发表时间：
2012-04-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Djuranovic S;Nahvi A;Green R
通讯作者：
Green R
DOI：
10.1073/pnas.84.19.6730
发表时间：
1987-10-01
影响因子：
11.1
作者：
HENTZE, MW;ROUAULT, TA;KLAUSNER, RD
通讯作者：
KLAUSNER, RD
影响因子：
4.5
作者：
Holtz, Janette;Pasquinelli, Amy E.
通讯作者：
Pasquinelli, Amy E.
影响因子：
30.8
作者：
Chen, JF;Mandel, EM;Wang, DZ
通讯作者：
Wang, DZ