Abstract
Nuclear Argonaute proteins, guided by small RNAs, mediate sequence-specific heterochromatin formation. The molecular principles that link Argonaute-small RNA complexes to cellular heterochromatin effectors on binding to nascent target RNAs are poorly understood. Here, we explain the mechanism by which the PIWI-interacting RNA (piRNA) pathway connects to the heterochromatin machinery in Drosophila. We find that Panoramix, a corepressor required for piRNA-guided heterochromatin formation, is SUMOylated on chromatin in a Piwi-dependent manner. SUMOylation, together with an amphipathic LxxLL motif in Panoramix's intrinsically disordered repressor domain, are necessary and sufficient to recruit Small ovary (Sov), a multi-zinc-finger protein essential for general heterochromatin formation and viability. Structure-guided mutations that eliminate the Panoramix-Sov interaction or that prevent SUMOylation of Panoramix uncouple Sov from the piRNA pathway, resulting in viable but sterile flies in which Piwi-targeted transposons are derepressed. Thus, Piwi engages the heterochromatin machinery specifically at transposon loci by coupling recruitment of a corepressor to nascent transcripts with its SUMOylation.
© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Motifs
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Animals
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Animals, Genetically Modified
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Argonaute Proteins / genetics
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Argonaute Proteins / metabolism
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Binding Sites / genetics
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Chromatin / genetics
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Chromatin / metabolism
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DNA Transposable Elements
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Drosophila Proteins / chemistry
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Drosophila Proteins / genetics*
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / genetics
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Drosophila melanogaster / metabolism
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Female
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Gene Silencing
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Genes, Insect
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Heterochromatin / genetics*
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Heterochromatin / metabolism*
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Intrinsically Disordered Proteins / chemistry
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Intrinsically Disordered Proteins / genetics
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Intrinsically Disordered Proteins / metabolism
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Models, Molecular
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Mutation
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism*
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Oogonial Stem Cells / metabolism
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Protein Interaction Domains and Motifs
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RNA, Small Interfering / genetics*
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RNA, Small Interfering / metabolism*
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RNA-Binding Proteins / chemistry
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RNA-Binding Proteins / genetics*
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RNA-Binding Proteins / metabolism*
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Sumoylation / genetics
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Ubiquitin-Conjugating Enzymes / genetics
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Ubiquitin-Conjugating Enzymes / metabolism
Substances
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Argonaute Proteins
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Chromatin
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DNA Transposable Elements
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DNA-Binding Proteins
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Drosophila Proteins
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Heterochromatin
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Intrinsically Disordered Proteins
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Nuclear Proteins
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RNA, Small Interfering
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RNA-Binding Proteins
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panx protein, Drosophila
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sov protein, Drosophila
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Ubiquitin-Conjugating Enzymes
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ubiquitin-conjugating enzyme UBC9