PXD063298

PXD063298 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-24 15:36:27	ID requested
⏵ 1	2025-04-30 00:50:37	announced

Dataset with its publication pending

submitter keyword: TMTpro 18plex, ribosome, mTOR

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/04/PXD063298

PRIDE project URI

• PRIDE
  1. PXD063298
     1. Label: PRIDE project
     2. Name: A programmed decline in ribosome levels governs human early neurodevelopment