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Nucleic Acids Res. 2017 Jan 25;45(2):938-950. doi: 10.1093/nar/gkw792. Epub 2016 Sep 6.

Conservation of miRNA-mediated silencing mechanisms across 600 million years of animal evolution.

Author information

1
Non-coding RNAs and mechanisms of cytoplasmic gene regulation, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany.
2
Proteome dynamics, Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany.
3
Department of Ecology, Evolution and Behavior, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91905, Israel.
4
Non-coding RNAs and mechanisms of cytoplasmic gene regulation, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany marina.chekulaeva@mdc-berlin.de.

Abstract

Our current knowledge about the mechanisms of miRNA silencing is restricted to few lineages such as vertebrates, arthropods, nematodes and land plants. miRNA-mediated silencing in bilaterian animals is dependent on the proteins of the GW182 family. Here, we dissect the function of GW182 protein in the cnidarian Nematostella, separated by 600 million years from other Metazoa. Using cultured human cells, we show that Nematostella GW182 recruits the CCR4-NOT deadenylation complexes via its tryptophan-containing motifs, thereby inhibiting translation and promoting mRNA decay. Further, similarly to bilaterians, GW182 in Nematostella is recruited to the miRNA repression complex via interaction with Argonaute proteins, and functions downstream to repress mRNA. Thus, our work suggests that this mechanism of miRNA-mediated silencing was already active in the last common ancestor of Cnidaria and Bilateria.

PMID:
27604873
PMCID:
PMC5314787
DOI:
10.1093/nar/gkw792
[Indexed for MEDLINE]
Free PMC Article

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