PXD049966-2

PXD049966 is an original dataset announced via ProteomeXchange.

Title	Threonine fuels glioblastoma through YRDC-mediated codon-biased translational reprogramming
Description	Cancers commonly reprogram translation and metabolism, but little is known about how these two features coordinate in cancer stem cells. Here, we show that glioblastoma stem cells (GSCs) display elevated protein translation. To dissect underlying mechanisms, we performed a CRISPR screen and identified YRDC as the top essential tRNA modification enzymes in GSCs. YRDC catalyses the formation of N6-threonylcarbamoyladenosine (t6A) on ANN-decoding tRNAs (A denotes adenosine and N denotes any nucleotide). Targeting YRDC reduced t6A formation, suppressed global translation, and inhibited tumour growth both in vitro and in vivo. Threonine is an essential substrate of YRDC. Threonine accumulated in GSCs, which facilitated t6A formation through YRDC and shifted the proteome to support mitosis-related genes with ANN codon-bias. Dietary threonine restriction (TR) reduced tumour t6A formation, slowed xenograft growth, and augmented anti-tumour efficacy of chemotherapy and anti-mitotic therapy, providing a molecular basis for a dietary intervention in cancer treatment.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:31:29.503.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Soren Heissel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-20 08:33:26	ID requested
1	2024-02-22 06:30:44	announced
⏵ 2	2024-10-22 06:31:29	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: threonine, tRNA modification, YRDC,glioblastoma stem cells

Jeremy N Rich
contact affiliation	Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
contact email	drjeremyrich@gmail.com
lab head
Soren Heissel
contact affiliation	Research Support Specialist
contact email	sheissel@rockefeller.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/2024/02/PXD049966

PRIDE project URI

• PRIDE
  1. PXD049966
     1. Label: PRIDE project
     2. Name: Threonine fuels glioblastoma through YRDC-mediated codon-biased translational reprogramming