Panoramix SUMOylation on chromatin connects the piRNA pathway to the cellular heterochromatin machinery.
Amino Acid Motifs
Animals
Animals, Genetically Modified
Argonaute Proteins
/ genetics
Binding Sites
/ genetics
Chromatin
/ genetics
DNA Transposable Elements
DNA-Binding Proteins
/ chemistry
Drosophila Proteins
/ chemistry
Drosophila melanogaster
/ genetics
Female
Gene Silencing
Genes, Insect
Heterochromatin
/ genetics
Intrinsically Disordered Proteins
/ chemistry
Models, Molecular
Mutation
Nuclear Proteins
/ chemistry
Oogonial Stem Cells
/ metabolism
Protein Interaction Domains and Motifs
RNA, Small Interfering
/ genetics
RNA-Binding Proteins
/ chemistry
Sumoylation
/ genetics
Ubiquitin-Conjugating Enzymes
/ genetics
Journal
Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
17
06
2021
accepted:
30
12
2021
entrez:
17
2
2022
pubmed:
18
2
2022
medline:
26
2
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35173350
doi: 10.1038/s41594-022-00721-x
pii: 10.1038/s41594-022-00721-x
doi:
Substances chimiques
Argonaute Proteins
0
Chromatin
0
DNA Transposable Elements
0
DNA-Binding Proteins
0
Drosophila Proteins
0
Heterochromatin
0
Intrinsically Disordered Proteins
0
Nuclear Proteins
0
RNA, Small Interfering
0
RNA-Binding Proteins
0
panx protein, Drosophila
0
sov protein, Drosophila
0
Ubiquitin-Conjugating Enzymes
EC 2.3.2.23
ubiquitin-conjugating enzyme UBC9
EC 6.3.2.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
130-142Subventions
Organisme : NIGMS NIH HHS
ID : P30 GM124165
Pays : United States
Organisme : NIH HHS
ID : S10 OD021527
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.
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