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PXD046381

PXD046381 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePre-mRNA fate decision by TTP safeguards the fidelity of the inflammatory response
DescriptionSuccessful immune responses are dependent on a precisely controlled balance between transcription and mRNA degradation. mRNA decay is driven through RNA-binding proteins (RBP), yet it remains unclear, how and when an individual mRNA molecule is selected for degradation. We investigated this fundamental question by using the anti-inflammatory RBP tristetraprolin (TTP, also known as Zfp36) as a model. Here, we show that TTP determines the fate of its targets concomitantly with their synthesis by binding to the pre-mRNA in the nucleus. Furthermore, we provide evidence that TTP orchestrates the target destabilization via a hierarchical molecular assembly that culminates by the association of mature mRNA with the RNA degradation machinery in the cytoplasm. The early fate decision in the life cycle of a TTP target mRNA prevents the translation of inflammatory mediators, particularly cytokine mRNAs, and promotes efficient cessation of the immune response. Importantly, the TTP homolog ZFP36L1 displays similar characteristics, suggesting a conserved mode of action within the ZFP36 family of RBPs.
HostingRepositoryPRIDE
AnnounceDate2025-01-27
AnnouncementXMLSubmission_2025-01-27_01:04:27.702.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterWeiQiang Chen
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Exploris 480; Q Exactive HF-X
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-10-25 03:49:35ID requested
12025-01-27 01:04:28announced
Publication List
10.1016/J.MOLCEL.2025.01.001;
Keyword List
submitter keyword: mRNA decay, pre-mRNA binding, resolution of inflammation,Inflammation, TTP
Contact List
Pavel Kovarik
contact affiliationMax Perutz Labs, Campus Vienna Biocenter 5, 1030 Vienna
contact emailpavel.kovarik@univie.ac.at
lab head
WeiQiang Chen
contact affiliationMass Spectrometry Facility, Max Perutz Laboratories Support GmbH
contact emailchenweiqiang@gmail.com
dataset submitter
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Dataset FTP location
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