PXD011979

PXD011979 is an original dataset announced via ProteomeXchange.

Title	An oxygen-sensing network of RNA-binding proteins controls glycolysis via hypoxic translatome remodeling.
Description	System-wide remodeling of protein synthesis is a keystone of cellular stress adaptation. Accumulating evidence suggests that changes in protein output (translatome) are controlled predominantly by translational mechanisms that restructure mRNA translation efficiencies (TEs), rather than simple fluctuations in mRNA expression. At the core of this phenomenon lies the key outstanding issue as to the drivers of such stimuli-induced translatome reprogramming, especially from an unbiased, systemic perspective. Oxygen deficiency (hypoxia) is frequently encountered in health and disease. In this study, we report the RNA-binding protein (RBP) nexus that governs oxygen-sensitive translatome reprogramming. Global MATRIX analysis produced an impartial, activity-based blueprint of dynamic RBP utilization, revealing hypoxia-augmented translational activities of HuR hnRNP A2/B1, PCBP1, PCBP2, and PTBP1. Translatome analysis by TMT-pSILAC of each aforementioned RBP revealed a synergistic network that effectuates oxygen-dependent translatome reorganization to enable hypoxic adaptation. Specifically, each RBP is tasked with activating a distinct portfolio of targets and cellular processes that synergistically contribute toward a comprehensive hypoxic response. Notably, the activation of glycolysis and hypoxic cell survival are critically dependent on this RBP network. The hypoxia-inducible factor 2α (HIF-2α) operates as the critical translation-regulating oxygen-sensor that collaborates with this RBP network to regulate mRNA TE and steady-state levels. These observations reveal an RBP/HIF-2α axis that restructures protein output in response to oxygen fluctuations. Conceptually, these findings demonstrate that stress-sensing RBP networks act as gatekeepers of mRNA utilization for global translational remodeling.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:08:19.335.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jonathan Krieger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2018-12-07 02:01:46	ID requested
1	2020-07-01 22:23:06	announced
⏵ 2	2024-10-22 05:08:21	announced	2024-10-22: Updated project metadata.

Ho JJD, Balukoff NC, Theodoridis PR, Wang M, Krieger JR, Schatz JH, Lee S, A network of RNA-binding proteins controls translation efficiency to activate anaerobic metabolism. Nat Commun, 11(1):2677(2020) [pubmed]

10.1038/s41467-020-16504-1;

curator keyword: Biological, Biomedical

submitter keyword: PCBP2, PCBP1,Translation, hypoxia, PTBP1, hnRNP A2/B1, HuR, HIF, glycolysis, HIF-2α

Stephen Lee
contact affiliation	Professor Director, Executive Ph.D. Program Department of Biochemistry & Molecular Biology Sylvester Comprehensive Cancer Center Miller School of Medicine University of Miami Gauthier Build, room 216 Laboratory, rooms 215, 218, 225 Miami, FL 33101-6129 Tel: (305) 243-5177 cell: (305) 877-9731
contact email	stephenlee@med.miami.edu
lab head
Jonathan Krieger
contact affiliation	Bruker
contact email	JRKrieger@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/2020/07/PXD011979

PRIDE project URI

• PRIDE
  1. PXD011979
     1. Label: PRIDE project
     2. Name: An oxygen-sensing network of RNA-binding proteins controls glycolysis via hypoxic translatome remodeling.