PXD046963-2

PXD046963 is an original dataset announced via ProteomeXchange.

Title	KDM5-mediated transcriptional activation of ribosomal protein genes alters translation efficiency to regulate mitochondrial metabolism
Description	Genes encoding the KDM5 family of transcriptional regulators are disrupted in individuals with intellectual disability (ID). To understand the link between KDM5 and ID, we generated five Drosophila strains harboring missense alleles analogous to those observed in patients. These alleles showed effects on neuroanatomical development, cognition, and other behaviors, in addition to a transcriptional signature that included the downregulation of many ribosomal protein genes. A similar transcriptional profile was observed in KDM5C knockout human glutamatergic neurons derived from induced pluripotent stem cells (iPSCs), suggesting a conserved role for KDM5 proteins in regulating ribosomal protein genes. Quantifying changes to the translatome caused by reduced KDM5 in Drosophila neurons, we find that the translation of mRNAs required for mitochondrial activity was particularly affected. Altered mitochondrial activity was confirmed through metabolomic studies that revealed decreased citric acid cycle activity. KDM5 therefore plays a key role in maintaining mitochondrial function that, when altered, could contribute to cognitive and behavioral phenotypes.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:14:21.290.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Simone Sidoli
SpeciesList	scientific name: Drosophila melanogaster (Fruit fly); NCBI TaxID: 7227;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-14 14:55:47	ID requested
1	2023-11-14 15:35:12	announced
⏵ 2	2024-10-22 06:14:21	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Ribosome, neuron,KDM5, brain, iPSCs, Translation, Transcription, KDM5C, Histone demethylase, Ribo-seq

Simone Sidoli
contact affiliation	Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, United States
contact email	simone.sidoli@einsteinmed.edu
lab head
Simone Sidoli
contact affiliation	Albert Einstein College of Medicine
contact email	simone.sidoli@gmail.com
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/2023/11/PXD046963

PRIDE project URI

• PRIDE
  1. PXD046963
     1. Label: PRIDE project
     2. Name: KDM5-mediated transcriptional activation of ribosomal protein genes alters translation efficiency to regulate mitochondrial metabolism