Mauri Marta, Kirchner Marieluise, Aharoni Reuven, Ciolli Mattioli Camilla, van den Bruck David, Gutkovitch Nadya, Modepalli Vengamanaidu, Selbach Matthias, Moran Yehu, Chekulaeva Marina
Non-coding RNAs and mechanisms of cytoplasmic gene regulation, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany.
Proteome dynamics, Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany.
Nucleic Acids Res. 2017 Jan 25;45(2):938-950. doi: 10.1093/nar/gkw792. Epub 2016 Sep 6.
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.
我们目前对miRNA沉默机制的了解仅限于少数几个谱系，如脊椎动物、节肢动物、线虫和陆地植物。在两侧对称动物中，miRNA介导的沉默依赖于GW182家族的蛋白质。在这里，我们剖析了刺胞动物海葵中GW182蛋白的功能，海葵与其他后生动物在6亿年前就已分化。利用培养的人类细胞，我们发现海葵GW182通过其含色氨酸的基序招募CCR4-NOT去腺苷酸化复合体，从而抑制翻译并促进mRNA降解。此外，与两侧对称动物类似，海葵中的GW182通过与AGO蛋白相互作用被招募到miRNA抑制复合体中，并在下游发挥作用以抑制mRNA。因此，我们的研究表明，这种miRNA介导的沉默机制在刺胞动物和两侧对称动物的最后一个共同祖先中就已经发挥作用。
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