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PXD013611 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePRMT5 methylome profiling uncovers a direct link to splicing regulation in human acute myeloid leukemia
DescriptionProtein arginine methyltransferase 5 (PRMT5) belongs to the class II arginine methyltransferases and catalyzes monomethylation and symmetrical dimethylation of arginines on proteins. It has recently emerged as a promising cancer drug target, and two PRMT5 inhibitors are currently in clinical trials for a range malignancies. Despite the recognized therapeutic potential, it is unclear which PRMT5 functions underlie its oncogenic activity. In this study, we aimed to further understand the role of PRMT5 in acute myeloid leukemia (AML). Using an enzymatic dead version of PRMT5 as well as a PRMT5-specific inhibitor, we demonstrated the requirement of the catalytic activity of PRMT5 for the survival of AML cells. By using cutting-edge proteomics techniques we identified PRMT5 substrates and investigated their role in the survival of AML cells. We found that the function of the splicing regulator SRSF1 relies on its methylation by PRMT5. Consistent with this, we found that loss of PRMT5 led to changes in alternative splicing. This revealed multiple affected essential genes, linking PRMT5 activity to its loss of function phenotype. Our results show that PRMT5 directly regulates SRSF1 activity in leukemia, and they provide potential biomarkers for the treatment response to PRMT5 inhibitors.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPavel Shliaha
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; monomethylated residue; dimethylated residue; iodoacetamide derivatized residue; deamidated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-04-23 09:02:11ID requested
12019-11-08 09:01:19announced
Publication List
Radzisheuskaya A, Shliaha PV, Grinev V, Lorenzini E, Kovalchuk S, Shlyueva D, Gorshkov V, Hendrickson RC, Jensen ON, Helin K, PRMT5 methylome profiling uncovers a direct link to splicing regulation in acute myeloid leukemia. Nat Struct Mol Biol, 26(11):999-1012(2019) [pubmed]
Keyword List
submitter keyword: human, PRMT5, arginine methylation, TMT, PTM
Contact List
Ole N Jensen
contact affiliationDepartment of Biochemistry and Molecular Biology, VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, Campusvej 55, DK - 5230 Odense M, Denmark
contact emailjenseno@bmb.sdu.dk
lab head
Pavel Shliaha
contact affiliationSyddansk University
contact emailpavels@bmb.sdu.dk
dataset submitter
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