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The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC

Abstract

Since their discovery almost two decades ago, microRNAs (miRNAs) have been shown to function by post-transcriptionally regulating protein accumulation. Understanding how miRNAs silence targeted mRNAs has been the focus of intensive research. Multiple models have been proposed, with few mechanistic details having been worked out. However, the past few years have witnessed a quantum leap forward in our understanding of the molecular mechanics of miRNA-mediated gene silencing. In this review we describe recent discoveries, with an emphasis on how miRISC post-transcriptionally controls gene expression by inhibiting translation and/or initiating mRNA decay, and how trans-acting factors control miRNA action.

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Figure 1: miRISC-mediated gene silencing.
Figure 2: Schematic diagram of GW182 and its interaction partners.
Figure 3: A temporal model of miRNA-mediated gene silencing.
Figure 4: Schematic of 3′ UTR binding proteins modulating miRNA target site accessibility.

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Acknowledgements

This work was supported by a grant from the Canadian Institutes of Health Research (MOP93607 to N.S.). We thank W. Filipowicz, and current and past members of the Sonenberg lab for insightful comments. We also thank R. Green and A. Giraldez for sharing unpublished data.

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Fabian, M., Sonenberg, N. The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat Struct Mol Biol 19, 586–593 (2012). https://doi.org/10.1038/nsmb.2296

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