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PXD055904

PXD055904 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleNeuronal aging leads to disrupted RNA metabolism
DescriptionAging is one of the most prominent risk factors for neurodegeneration, yet the molecular mechanisms underlying the deterioration of old neurons are mostly unknown. To efficiently study neurodegeneration in the context of aging, we transdifferentiated primary human fibroblasts from aged (i.e. >50 year-old) healthy donors directly into neurons, which retained their aging-associated phenotypes including senescence and dysregulation of CpG methylation. Here we show that aged neurons are broadly depleted of RNA-binding proteins, especially 26 spliceosome components. Intriguingly, splicing proteins – like the dementia and ALS-associated protein TDP-43 – mislocalize to the cytoplasm in aged neurons, which leads to widespread alternative splicing. Although spliceosome components can be sequestered within cytoplasmic stress granules, we find that aged neurons suffer from chronic stress that leads to the segregation of stress granule and spliceosome RNA-binding proteins. We link chronic stress to the accumulation of misfolded proteins and to poor HSP90α chaperone activity. Importantly, we also show that aged neurons respond poorly to acute stress treatments, leading to long-term retention of stress granules and failure to initiate transcription of stress-related heat shock proteins. Together our data demonstrates that dysregulation of RNA metabolism is a key driver of poor resiliency in aged neurons.
HostingRepositoryPRIDE
AnnounceDate2025-02-19
AnnouncementXMLSubmission_2025-02-18_17:25:01.583.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterXuezhen Ge
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-09-16 07:58:51ID requested
12025-02-18 17:25:01announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Human, neuron, transdifferentiation
Contact List
Gene W. Yeo
contact affiliationDepartment of Cellular & Molecular Medicine, University of California, San Diego, CA 92093, USA.
contact emailgeneyeo@ucsd.edu
lab head
Xuezhen Ge
contact affiliationUniversity of California San Diego
contact emailx1ge@ucsd.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
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