PXD061852

PXD061852 is an original dataset announced via ProteomeXchange.

Title	Endogenous retrovirus-like proteins recruit UBQLN2 to stress granules and shape their functional biology
Description	The human genome is replete with sequences derived from foreign elements including endogenous retrovirus-like proteins of unknown function. The human genome is replete with sequences derived from foreign elements including endogenous retrovirus-like proteins of unknown function. Here we show that UBQLN2, a ubiquitin-proteasome shuttle factor implicated in neurodegenerative diseases, is regulated by the linked actions of two retrovirus-like proteins, RTL8 and PEG10. RTL8 confers on UBQLN2 the ability to complex with and regulate PEG10. PEG10, a core component of stress granules, drives the recruitment of UBQLN2 to stress granules under various stress conditions, but can only do so when RTL8 is present. Changes in PEG10 levels further remodel the kinetics of stress granule disassembly and overall composition by incorporating select extracellular vesicle proteins. Within stress granules, PEG10 forms virus-like particles, underscoring the structural heterogeneity of this class of biomolecular condensates. Together, these results reveal an unexpected link between pathways of cellular proteostasis and endogenous retrovirus-like proteins. we show that UBQLN2, a ubiquitin-proteasome shuttle factor implicated in neurodegenerative diseases, is regulated by the linked actions of two retrovirus-like proteins, RTL8 and PEG10. RTL8 confers on UBQLN2 the ability to complex with and regulate PEG10. PEG10, a core component of stress granules, drives the recruitment of UBQLN2 to stress granules under various stress conditions, but can only do so when RTL8 is present. Changes in PEG10 levels further remodel the kinetics of stress granule disassembly and overall composition by incorporating select extracellular vesicle proteins. Within stress granules, PEG10 forms virus-like particles, underscoring the structural heterogeneity of this class of biomolecular condensates. Together, these results reveal an unexpected link between pathways of cellular proteostasis and endogenous retrovirus-like proteins.
HostingRepository	PRIDE
AnnounceDate	2025-06-04
AnnouncementXML	Submission_2025-06-04_08:42:56.673.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lisa Sharkey
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion; Orbitrap Ascend

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-14 10:11:58	ID requested
⏵ 1	2025-06-04 08:42:57	announced

Dataset with its publication pending

submitter keyword: stress granules, retrotransposon-derived proteins,Ubiquilins

Lisa M. Sharkey
contact affiliation	Department of Neurology, University of Michigan Medical School, Ann Arbor, MI 48109, United States
contact email	lisams@umich.edu
lab head
Lisa Sharkey
contact affiliation	University of Michigan
contact email	lisams@umich.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD061852
     1. Label: PRIDE project
     2. Name: Endogenous retrovirus-like proteins recruit UBQLN2 to stress granules and shape their functional biology