PXD043342

PXD043342 is an original dataset announced via ProteomeXchange.

Title	RAVER1 interconnects lethal EMT and miR/RISC activity by the control of alternative splicing
Description	The RAVER1 protein was proposed to serve as a co-factor in guiding the PTBP-dependent control of alternative splicing (AS). Whether RAVER1 solely acts in concert with PTBPs and how it affects cancer cell fate remained elusive. Here we provide the first comprehensive investigation of RAVER1-controlled AS in cancer cell models and reveal a pro-oncogenic role of RAVER1 in tumor growth. This unravels that RAVER1 guides AS in synergy with PTBPs but more prominently serves PTBP1-independent roles in splicing. In cancer cells, one major function of RAVER1 is the control of proliferation and apoptosis, which involves the modulation of AS events within the miR/RISC pathway. Associated with this regulatory role, RAVER1 antagonizes lethal, TGFB-driven epithelial-mesenchymal-transition (EMT) by limiting TGFB signaling. RAVER1-modulated splicing events affect the insertion of protein interaction modules in factors guiding miR/RISC-dependent gene silencing. Most prominently, in all three human TNRC6 proteins, RAVER1 controls AS of GW-enriched motifs, which are essential for AGO2-binding. Disturbance of RAVER1-guided AS events in TNRC6 proteins and other facilitators of miR/RISC activity compromise miR/RISC activity which is essential to restrict TGFB signaling and lethal EMT.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:20:07.027.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD043342
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Christian Ihling
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-27 07:16:25	ID requested
1	2024-01-10 23:09:48	announced
⏵ 2	2024-10-22 06:20:07	announced	2024-10-22: Updated project metadata.

10.6019/PXD043342;

submitter keyword: cancer, EMT,RAVER1, TGFB, microRNA, PTBP, alternative splicing, RISC

Stefan Hüttelmaier
contact affiliation	Martin Luther University (MLU) Institute of Molecular Medicine (IMM) Sect. Molecular Cell Biology
contact email	stefan.huettelmaier@medizin.uni-halle.de
lab head
Christian Ihling
contact affiliation	MLU Halle, Inst. f. Pharmacy
contact email	christian.ihling@pharmazie.uni-halle.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043342
     1. Label: PRIDE project
     2. Name: RAVER1 interconnects lethal EMT and miR/RISC activity by the control of alternative splicing