PXD039447-1

PXD039447 is an original dataset announced via ProteomeXchange.

Title	Cancer Mutations Rewire the RNA Methylation Specificity of METTL3-METTL14
Description	Chemical modification of RNAs is important for post-transcriptional gene regulation. The METTL3-METTL14 complex generates most N6-methyladenosine (m6A) modifications in mRNAs, and dysregulated methyltransferase expression has been linked to numerous cancers. Here we show that m6A modification location, rather than the overall modification level, can impact oncogenesis. A gain-of-function missense mutation found in cancer patients, METTL14R298P, promotes malignant cell growth in culture and in transgenic mice. The mutant methyltransferase preferentially modifies noncanonical sites and transforms gene expression without increasing global m6A levels in mRNAs. The altered substrate specificity is intrinsic to METTL3-METTL14, helping us to propose a structural model for how the METTL3-METTL14 complex detects RNA sequences. Together, our work highlights that m6A location is important for function and that noncanonical methylation sites may impact aberrant gene expression and oncogenesis.
HostingRepository	PRIDE
AnnounceDate	2024-12-21
AnnouncementXML	Submission_2024-12-21_10:33:13.696.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yen-Yu Yang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-13 16:12:46	ID requested
⏵ 1	2024-12-21 10:33:14	announced

10.1126/SCIADV.ADS4750;

submitter keyword: oncogenesis,METTL3, m6A, METTL14, LC-MS/MS, HepG2

Yinsheng Wang
contact affiliation	Department of Chemistry, UC Riverside
contact email	yinsheng@ucr.edu
lab head
Yen-Yu Yang
contact affiliation	UC Riverside
contact email	yyang227@ucr.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/2024/12/PXD039447

PRIDE project URI

• PRIDE
  1. PXD039447
     1. Label: PRIDE project
     2. Name: Cancer Mutations Rewire the RNA Methylation Specificity of METTL3-METTL14