Drosophila Piwi distinguishes transposons from mRNAs by piRNA complementarity and abundance
Masaru Ariura,
Therese Solberg,
Hirotsugu Ishizu,
Hazuki Takahashi,
Piero Carninci,
Haruhiko Siomi,
Yuka W. Iwasaki
Affiliations
Masaru Ariura
Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan
Therese Solberg
Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan; Human Biology Microbiome Quantum Research Center (WPI-Bio2Q), Keio University, Tokyo, Japan
Hirotsugu Ishizu
Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan
Hazuki Takahashi
Laboratory for Transcriptome Technology, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan
Piero Carninci
Laboratory for Transcriptome Technology, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Human Technopole, Via Rita Levi Montalcini 1, Milan, Italy
Haruhiko Siomi
Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan; Human Biology Microbiome Quantum Research Center (WPI-Bio2Q), Keio University, Tokyo, Japan; Corresponding author
Yuka W. Iwasaki
Laboratory for Functional Non-coding Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan
Summary: Piwi-interacting RNAs (piRNAs) are the main repressors of transposable elements (TEs) in animal germlines. In Drosophila, Piwi-piRNA complexes associate with nascent TE transcripts to drive heterochromatin formation and TE repression. However, previous studies have shown that Piwi also associates with large numbers of mRNAs, raising the question of how Piwi discriminates between mRNAs and TEs. To answer this question, we performed a comprehensive analysis of Piwi-associated RNAs, compositionally and functionally, to decipher the targeting rules of Piwi-piRNA complexes. While Piwi initially identifies its targets through the seed sequence, it requires pairing well beyond the seed, nearly a perfect match, to elicit a repressive response. In addition to the complementarity of piRNAs to their targets, their abundance must reach a certain threshold to be functional. Together, these findings explain large differences in the target repression of Piwi-associated RNAs and reveal how Piwi efficiently distinguishes TEs from mRNAs despite associating with both.
