PXD063298 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | A programmed decline in ribosome levels governs human early neurodevelopment |
Description | How reductions in ribosome biogenesis can result in tissue- and developmental-specific defects remain a mystery. Here we describe allelic variants in the ribosome biogenesis factor AIRIM/C1orf109 that are primarily associated with neurodevelopmental disorders. Using human cerebral organoids in combination with proteomic, single-cell transcriptome across multiple developmental stages, and single-organoid translatome analyses, we identify a previously unappreciated drop in protein production during early brain development. We find ribosome levels decrease during neuroepithelial differentiation, making differentiating cells particularly vulnerable to perturbations in ribosome biogenesis during this time. Reduced ribosome availability more profoundly impacts the translation of specific transcripts, disrupting both survival and cell fate commitment of transitioning neuroepithelia. Enhancing mTOR activity by both genetic and pharmacologic methods suppresses the growth and developmental defects associated with intellectual disability linked variants. This work provides further evidence for the functional importance of regulated changes in global protein synthesis capacity during cellular differentiation. |
HostingRepository | PRIDE |
AnnounceDate | 2025-04-30 |
AnnouncementXML | Submission_2025-04-30_00:50:37.122.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Andrew Lemoff |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Eclipse |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2025-04-24 15:36:27 | ID requested | |
⏵ 1 | 2025-04-30 00:50:37 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: TMTpro 18plex, ribosome, mTOR |
Contact List
Michael Buszczak |
contact affiliation | Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 |
contact email | michael.buszczak@utsouthwestern.edu |
lab head | |
Andrew Lemoff |
contact affiliation | UT Southwestern Medical Center |
contact email | andrew.lemoff@utsouthwestern.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD063298
- Label: PRIDE project
- Name: A programmed decline in ribosome levels governs human early neurodevelopment