title: Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties.
abstract: SPT5 and its binding partner SPT4 function in both positively and negatively regulating transcriptional elongation. The demonstration that SPT5 and RNA polymerase II are targets for phosphorylation by CDK9/cyclin T1 indicates that posttranslational modifications of these factors are important in regulating the elongation process. In this study, we utilized a biochemical approach to demonstrate that SPT5 was specifically associated with the protein arginine methyltransferases PRMT1 and PRMT5 and that SPT5 methylation regulated its interaction with RNA polymerase II. Specific arginine residues in SPT5 that are methylated by these enzymes were identified and demonstrated to be important in regulating its promoter association and subsequent effects on transcriptional elongation. These results suggest that methylation of SPT5 is an important posttranslational modification that is involved in regulating its transcriptional elongation properties in response to viral and cellular factors.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas 75390, USA.
authors.forename: Youn Tae
authors.initials: YT
authors.lastname: Kwak
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.forename: Shashi
authors.initials: S
authors.lastname: Prajapati
authors.forename: Kyu-Jin
authors.initials: KJ
authors.lastname: Park
authors.forename: Rama M
authors.initials: RM
authors.lastname: Surabhi
authors.forename: Brady
authors.initials: B
authors.lastname: Miller
authors.forename: Peter
authors.initials: P
authors.lastname: Gehrig
authors.forename: Richard B
authors.initials: RB
authors.lastname: Gaynor
mesh_terms: D001120:Arginine / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone; D016207:Cytokines / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D005057:Eukaryotic Cells / Q000201:enzymology*; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011496:Protein Methyltransferases / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*; D035602:Transcriptional Elongation Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D016207:Cytokines; D035602:Transcriptional Elongation Factors; C069940:SPT5 transcriptional elongation factor; D001120:Arginine; D011496:Protein Methyltransferases; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases; D012319:RNA Polymerase II