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Translational Control of Endogenous MicroRNA Target Genes in C. elegans

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miRNA Regulation of the Translational Machinery

Part of the book series: Progress in Molecular and Subcellular Biology ((PMSB,volume 50))

Abstract

lin-4 and let-7 are the founding members of the large microRNA (miRNA) family of regulatory RNAs and were originally identified as components of a C. elegans developmental pathway that controls temporal cell fates. Consistent with their pioneering role, lin-4 and let-7 were studied widely as “model miRNAs” in efforts to reveal the mode of action of miRNAs. Early work on lin-4 thus established a paradigm that miRNAs inhibit translation of their target mRNAs at a step downstream from initiation, without affecting mRNA stability. Although some studies on mammalian miRNAs in cell culture reached similar conclusions, most of those studies indicated that miRNAs repressed translation initiation and frequently also promoted target mRNA degradation. We will discuss here what is known about modes of miRNA target gene repression in C. elegans, highlighting recent work that demonstrates that both mRNA degradation and repression of translation initiation are mechanisms employed in vivo by let-7 and, unexpectedly, lin-4 to silence their endogenous targets. We will also discuss the roles of the GW182 homologous AIN-1 and AIN-2 proteins in this process.

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Acknowledgments

X.D. was supported by a PhD student fellowship from the Boehringer Ingelheim Foundation. Research in H.G.’s lab is funded by the Novartis Research Foundation and the Swiss National Science Foundation.

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Authors and Affiliations

  1. Friedrich Miescher Institute for Biomedical Research (FMI), Maulbeerstrasse 66, WRO-1066.1.38, CH-4002, Basel, Switzerland

    Benjamin A. Hurschler, Xavier C. Ding & Helge Großhans

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  1. Benjamin A. Hurschler
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  2. Xavier C. Ding
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  3. Helge Großhans
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Correspondence to Helge Großhans .

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  1. Health Science Center, Dept. Biochemistry & Molecular Biology, Louisiana State University, Kings Highway 1501, Shreveport, 71130-3932, Louisiana, USA

    Robert E. Rhoads

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Hurschler, B.A., Ding, X.C., Großhans, H. (2010). Translational Control of Endogenous MicroRNA Target Genes in C. elegans . In: Rhoads, R. (eds) miRNA Regulation of the Translational Machinery. Progress in Molecular and Subcellular Biology(), vol 50. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-03103-8_2

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