The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements

Serena De Fazio, Nenad Bartonicek, Monica Di Giacomo, Cei Abreu-Goodger, Aditya Sankar, Charlotta Funaya, Claude Antony, Pedro N. Moreira, Anton J. Enright and Dónal O’Carroll ()
Additional contact information
Serena De Fazio: European Molecular Biology Laboratory, Mouse Biology Unit, Via Ramarini 32
Nenad Bartonicek: European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton
Monica Di Giacomo: European Molecular Biology Laboratory, Mouse Biology Unit, Via Ramarini 32
Cei Abreu-Goodger: European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton
Aditya Sankar: European Molecular Biology Laboratory, Mouse Biology Unit, Via Ramarini 32
Charlotta Funaya: European Molecular Biology Laboratory, EMBL Meyerhof Str. 1
Claude Antony: European Molecular Biology Laboratory, EMBL Meyerhof Str. 1
Pedro N. Moreira: European Molecular Biology Laboratory, Mouse Biology Unit, Via Ramarini 32
Anton J. Enright: European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton
Dónal O’Carroll: European Molecular Biology Laboratory, Mouse Biology Unit, Via Ramarini 32

Nature, 2011, vol. 480, issue 7376, 259-263

Abstract: Transposon silencing by Piwi proteins The combination of Piwi proteins and their associated Piwi-interacting RNAs (piRNAs) mediates epigenetic transposon silencing in animal germlines. Piwi proteins are predicted to be endonucleases, but the significance of this activity had not been demonstrated in vivo. The laboratories of Dónal O'Carroll and Ramesh Pillai have now made mouse models in which residues expected to be critical for nuclease activity in the three mouse Piwi homologues, Mili, Miwi and Miwi2, are mutated. The mutant mice show phenotypic differences. The Mili and Miwi mutants are defective in piRNA production, transposon silencing and fertility, whereas the Miwi2 mutant has normal piRNA levels, seems to undergo piRNA amplification and silences transposons. These studies highlight distinctions between the murine enzymes responsible for piRNA biogenesis.

Date: 2011
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DOI: 10.1038/nature10547

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