Conservation of miRNA-mediated silencing mechanisms across 600 million years of animal evolution.
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.
Non-coding RNAs and mechanisms of cytoplasmic gene regulation, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany.
Marta
M
Mauri
Proteome dynamics, Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany.
Marieluise
M
Kirchner
Department of Ecology, Evolution and Behavior, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91905, Israel.
Reuven
R
Aharoni
Non-coding RNAs and mechanisms of cytoplasmic gene regulation, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany.
Camilla
C
Ciolli Mattioli
Non-coding RNAs and mechanisms of cytoplasmic gene regulation, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany.
David
D
van den Bruck
Department of Ecology, Evolution and Behavior, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91905, Israel.
Nadya
N
Gutkovitch
Department of Ecology, Evolution and Behavior, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91905, Israel.
Vengamanaidu
V
Modepalli
Proteome dynamics, Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany.
Matthias
M
Selbach
Department of Ecology, Evolution and Behavior, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91905, Israel.
Yehu
Y
Moran
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.
Marina
M
Chekulaeva
D000818:Animals; D002460:Cell Line; D019143:Evolution, Molecular; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009690:Nucleic Acid Conformation; D059372:Nucleotide Motifs; D011485:Protein Binding; D034622:RNA Interference; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics
D035683:MicroRNAs; D012333:RNA, Messenger