Proteomics Data for "PRMT5 methylome profiling uncovers a direct link to splicing regulation in human acute myeloid leukemia"

UID: 10515

Author(s): Shliaha, Pavel*, Jensen, Ole N * MSK affiliated

Description: Summary from ProteomeXchange: "Protein 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."

Subject of Study

Subject(s)

OncoTree Cancer Type(s)

Acute Myeloid Leukemia

Access via ProteomeXchange
Standardized consortial metadata with links to data in original proteomics repository.
Accession #: PXD013611

Access via PRIDE
FASTA and RAW files.
Accession #: PXD013611
Access Restrictions: Free to All
Access Instructions: Public PXD datasets can be browsed over at ProteomeCentral.
All public datasets available in PRIDE Archive in the repository can be accessed via the website, Web Service (for programmatic access), and the PRIDE Inspector stand-alone tool.
Associated Publications: Radzisheuskaya A, Shliaha P, Grinev V, et al. PRMT5 methylome profiling uncovers a direct link to splicing regulation in acute myeloid leukemia. Nature Structural and Molecular Biology. 2019; 26(11):999-1012.
Data Type: Genomic
Equipment Used: Orbitrap Fusion Lumos
Dataset Format(s): XML, FASTA, PDResult, RAW
Dataset Size: FASTA (13MB), XML (742 MB), PDResult file (31GB), and 149 RAW files (100-1500 MB each).

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