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Pervasive SUMOylation of heterochromatin and piRNA pathway proteins

Ninova, Maria and Lomenick, Brett and Fejes-Tóth, Katalin and Aravin, Alexei A. (2022) Pervasive SUMOylation of heterochromatin and piRNA pathway proteins. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20220816-201512000

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Abstract

Genome regulation involves complex and highly regulated protein interactions that are often mediated through post-translational modifications (PTMs). SUMOylation - the covalent attachment of the small ubiquitin-like modifier (SUMO) - is a conserved PTM in eukaryotes that has been implicated in a number of essential processes such as nuclear import, DNA damage repair, transcriptional control, and chromatin organization. In Drosophila, SUMO is essential for viability and its depletion from the female germline causes infertility associated with global loss of heterochromatin, and illicit upregulation of transposons and lineage-inappropriate genes. However, the specific targets of SUMO and its mechanistic role in different cellular pathways are still poorly understood. Here, we developed a proteomics-based strategy to characterize the SUMOylated proteome in Drosophila that allowed us to identify ~1500 SUMO sites in 843 proteins in the fly ovary. A high confidence set of SUMOylated proteins is highly enriched in factors involved in heterochromatin regulation and the piRNA pathway that represses transposons. Furthermore, SUMOylation of several piRNA pathway proteins occurs in a Piwi-dependent manner, indicating a functional implication of this modification in the cellular response to transposon activity. Together, these data highlight the impact of SUMOylation on epigenetic regulation and reveal an unexpectedly broad role of the SUMO pathway in the cellular defense against genomic parasites. Finally, this work provides a valuable resource and a system that can be adapted to the study of SUMOylation in other Drosophila tissues.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2022.08.15.504007DOIDiscussion Paper
https://www.biorxiv.org/content/10.1101/2022.08.15.504007v1.supplementary-materialPublisherSupporting Information
ORCID:
AuthorORCID
Ninova, Maria0000-0001-5051-5502
Lomenick, Brett0000-0002-5023-9998
Fejes-Tóth, Katalin0000-0001-6558-2636
Aravin, Alexei A.0000-0002-6956-8257
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. We thank former Caltech Protein Exploration Laboratory (PEL) members Dr. Michael Sweredoski and Dr. Annie Moradian for their advice on diGly proteomics, and Corinne Karalun (former laboratory assistant in MN laboratory, UCR), Hannah Ryon (former rotation student in KFT laboratory, Caltech), Hannah Holmes and Matea Ibrahim (undergraduate students in UC Riverside) for assistance with Western Blotting, fly dissections and genotyping. This work was supported by grants from the NIH (K99/R00 HD099316) to MN; the NIH (R01 GM097363), the Ministry of Education and Science of the Russian Federation (14.W03.31.0007), and the Packard Fellowship Awards to AAA, and the NIH (R01GM110217) and Ellison Medical Foundation Awards to KFT. Authors contributions. MN, KFT and AAA conceptualized the proteomics study. MN designed and performed experiments, data curation and formal analysis, except LC-MS/MS runs and raw data processing which were performed at the Caltech PEL facility by BL. MN prepared figures and drafted the manuscript. MN and AAA edited the manuscript. The authors have declared no competing interest.
Funders:
Funding AgencyGrant Number
NIHK99/R00 HD099316
NIHR01 GM097363
Ministry of Education and Science of the Russian Federation14.W03.31.0007
David and Lucile Packard FoundationUNSPECIFIED
NIHR01 GM110217
Ellison Medical FoundationUNSPECIFIED
Subject Keywords:SUMO, piRNAs, heterochromatin, transposons, proteomics
DOI:10.1101/2022.08.15.504007
Record Number:CaltechAUTHORS:20220816-201512000
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20220816-201512000
Official Citation:Pervasive SUMOylation of heterochromatin and piRNA pathway proteins Maria Ninova, Brett Lomenick, Katalin Fejes-Tóth, Alexei A Aravin bioRxiv 2022.08.15.504007; doi: https://doi.org/10.1101/2022.08.15.504007
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:116301
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:16 Aug 2022 19:32
Last Modified:16 Aug 2022 19:32

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