PXD072448

PXD072448 is an original dataset announced via ProteomeXchange.

Title	Mechanism of protein abundance-independent 3′UTR-regulated JMJD3 activity in human cells
Description	The 3′UTR in the KDM6B mRNA can control the cellular activity of the produced KDM6B/JMJD3 protein, but the mechanism is unclear. To examine whether 3′UTR-dependent JMJD3 protein complexes are responsible for the observed 3′UTR-dependent protein activity, KDM6B cDNA expression constructs with or without the KDM6B 3′UTR were transfected into HeLa cells grown in SILAC media, followed by co-IP of the HA-tagged JMJD3 protein. Cells were grown in SILAC medium for 5 passages and were validated for amino acid incorporation before the experiment. We did not detect major differences in JMJD3 protein interactors, when JMJD3 was translated from mRNA templates with or without its 3′UTR. To investigate if the KDM6B 3′UTR controls JMJD3 activity through differences in protein folding, we performed XL-MS in cells expressing HA-tagged JMJD3 from an mRNA template with or without its 3′UTR. JMJD3 has a long intrinsically disordered region (IDR), containing more than 1100 amino acids and a structured JmjC domain at the C-terminus. Only in the presence of the long IDR is the activity of JMJD3 protein dependent on the 3′UTR. XL-MS revealed that translation of JMJD3 from an mRNA template with the 3′UTR changes co-translational protein folding in cells. When the protein was expressed in the presence of the 3′UTR, the majority of unique XL map to IDR-IDR interactions, whereas lack of the 3′UTR significantly increased the number of crosslinks involving the structured, enzymatic domain, which is consistent with reduced protein activity, likely caused by co-translational misfolding.
HostingRepository	PRIDE
AnnounceDate	2026-09-07
AnnouncementXML	Submission_2026-09-07_04:24:51.458.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhuoning Li
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-26 17:56:59	ID requested
⏵ 1	2026-09-07 04:24:52	announced

10.1016/j.cell.2026.05.017;

Luo Y, Zhong Y, Basu S, Wu MC, Mayr C, mRNA 3' UTRs chaperone intrinsically disordered regions to control protein activity. Cell, 189(15):4619-4636.e16(2026) [pubmed]

submitter keyword: None

Christine Mayr
contact affiliation	Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
contact email	mayrc@mskcc.org
lab head
Zhuoning Li
contact affiliation	MSKCC
contact email	liz2@mskcc.org
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/2026/09/PXD072448

PRIDE project URI

• PRIDE
  1. PXD072448
     1. Label: PRIDE project
     2. Name: Mechanism of protein abundance-independent 3′UTR-regulated JMJD3 activity in human cells