PXD059083

PXD059083 is an original dataset announced via ProteomeXchange.

Title	Meta-unstable mRNAs in activated CD8+ T cells are defined by interlinked AU-rich elements and m6A mRNA methylation
Description	CD8 ⁺ T cells can rapidly produce effector molecules following activation. This activation triggers fast changes in gene expression that rely on control of mRNA levels via multiple transcriptional and post-transcriptional mechanisms, including RNA modifications. N ⁶ -methyladenosine (m ⁶ A) is an abundant post-transcriptional modification that promotes the decay of messenger RNAs in the cytosol. How recognition of m ⁶ A sites is integrated with other regulatory mechanisms that alter the fate of immunoregulatory mRNAs in CD8 ⁺ T cells remains unexplored. Here, we applied the m ⁶ A-iCLIP (miCLIP) method and identified m ⁶ A antibody binding in RRACH and in AU-rich (ARE) motifs within 3’UTRs of CD8 ⁺ T cell mRNAs. The combined miCLIP signal in both motifs defined and predicted meta-unstable mRNAs that rapidly decayed upon CD8 ⁺ T cell activation. We demonstrate that mutations in the identified AREs are epistatic with RRACH mutations in their effects on TNF mRNA stability. Notably, the AREs in these mRNAs show enriched iCLIP crosslinking of YTHDF proteins, which were also identified by proteomic analyses of methylated ARE sequences along with additional novel RNA-binding proteins. Our study thus reveals a hitherto unexplored regulatory layer that interlinks m ⁶ A and ARE biology in CD8 ⁺ T cells, providing new approaches for modulating mRNA decay through m ⁶ A and ARE sites.
HostingRepository	PRIDE
AnnounceDate	2025-11-25
AnnouncementXML	Submission_2025-11-25_05:54:30.854.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Aniek Martens
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-20 02:35:00	ID requested
⏵ 1	2025-11-25 05:54:31	announced

Dataset with its publication pending

submitter keyword: None

Jernej Ule
contact affiliation	The Francis Crick Institute, 1 Midland Road, NW1 1AT London, UK; UCL Queen Square Institute of Neurology, QueenSquare, WC1N 3BG London, UK; National Institute of Chemistry, Hajdrihova 19, 1001 Ljubljana, Slovenia
contact email	jernej.ule@crick.ac.uk
lab head
Aniek Martens
contact affiliation	Oncode Institute, 3521 AL Utrecht, The Netherlands; Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University, 6525 GA Nijmegen, The Netherlands
contact email	aniek.martens@ru.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059083
     1. Label: PRIDE project
     2. Name: Meta-unstable mRNAs in activated CD8+ T cells are defined by interlinked AU-rich elements and m6A mRNA methylation