Direct interaction of Su(var)2-10 via the SIM-binding site of the Piwi protein is required for transposon silencing in Drosophila melanogaster

• Published in: The FEBS journal Vol. 291; no. 8; pp. 1759 - 1779
• Main Authors: Bence, Melinda, Jankovics, Ferenc, Kristó, Ildikó, Gyetvai, Ákos, Vértessy, Beáta G, Erdélyi, Miklós
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.04.2024
• Subjects: Binding sites; Derepression; Drosophila; Fruit flies; Gene silencing; Heterochromatin; Insects; Molecular modelling; Protein structure; Proteins; SUMO protein; Transposons; sumoylation; PIWI/piRNA; Drosophila melanogaster; Su(var)2‐10; transposon silencing
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.17073

Nuclear Piwi/Piwi-interacting RNA complexes mediate co-transcriptional silencing of transposable elements by inducing local heterochromatin formation. In Drosophila, sumoylation plays an essential role in the assembly of the silencing complex; however, the molecular mechanism by which the sumoylation machinery is recruited to the transposon loci is poorly understood. Here, we show that the Drosophila E3 SUMO-ligase Su(var)2-10 directly binds to the Piwi protein. This interaction is mediated by the SUMO-interacting motif-like (SIM-like) structure in the C-terminal domain of Su(var)2-10. We demonstrated that the SIM-like structure binds to a special region found in the MID domain of the Piwi protein, the structure of which is highly similar to the SIM-binding pocket of SUMO proteins. Abrogation of the Su(var)2-10-binding surface of the Piwi protein resulted in transposon derepression in the ovary of adult flies. Based on our results, we propose a model in which the Piwi protein initiates local sumoylation in the silencing complex by recruiting Su(var)2-10 to the transposon loci.