title: PRMT2 interacts with splicing factors and regulates the alternative splicing of BCL-X.
abstract: Protein arginine N-methyltransferase 2 (PRMT2) functions in JAK-STAT and Wnt/β-catenin signalling pathways, serves as a nuclear receptor-dependent transcriptional co-activator, and represses NF-κB and E2F1 transcription factor activities to promote apoptosis. We have previously demonstrated that PRMT2 interacts with PRMT1 and increases its activity. Here, we reveal associations using proteomics between the PRMT2 SH3 domain and splicing factors including Src-associated in mitosis 68 kDa protein (SAM68), a PRMT1 substrate and trans-acting factor that mediates BCL-X alternative splicing. We determined that PRMT2 interacts with SAM68 in cells and regulates its subcellular localization via the SH3 domain of PRMT2, prompting us to investigate the potential role of PRMT2 in BCL-X alternative splicing. We found that the expression of the full-length, wildtype form of PRMT2 promotes an increase in the BCL-X(L)/BCL-X(s) ratio in TNF-α or LPS stimulated cells. These results indicate that active PRMT2 may play a role during inflammation in alternative splicing regulation.
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Mynol I
authors.initials: MI
authors.lastname: Vhuiyan
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Magnolia L
authors.initials: ML
authors.lastname: Pak
authors.affiliation: Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Park
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Dylan
authors.initials: D
authors.lastname: Thomas
authors.affiliation: College of Pharmacy, Pharmaceutical Analysis Laboratory, The University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada.
authors.forename: Ted M
authors.initials: TM
authors.lastname: Lakowski
authors.affiliation: Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298, USA.|Hunter Holmes McGuire Veterans Administration Medical Center, Richmond, VA 23224, USA.|The Massey Cancer Center, Richmond, VA 23298, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Chalfant
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Adam
authors.initials: A
authors.lastname: Frankel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D017398:Alternative Splicing / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases / Q000737:chemistry / Q000378:metabolism*; D040901:Proteomics; D000072260:RNA Splicing Factors / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C489559:KHDRBS1 protein, human; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D051020:bcl-X Protein; C077013:PRMT2 protein, human; D011484:Protein-Arginine N-Methyltransferases
keywords: BCL-X; PRMT2; SAM68; SH3 domain; alternative splicing