Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties

Youn Tae Kwak; Jun Guo; Shashi Prajapati; Kyu-Jin Park; Rama M Surabhi; Brady Miller; Peter Gehrig; Richard B Gaynor

doi:10.1016/s1097-2765(03)00101-1

Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties

Mol Cell. 2003 Apr;11(4):1055-66. doi: 10.1016/s1097-2765(03)00101-1.

Authors

Youn Tae Kwak¹, Jun Guo, Shashi Prajapati, Kyu-Jin Park, Rama M Surabhi, Brady Miller, Peter Gehrig, Richard B Gaynor

Affiliation

¹ Division of Hematology-Oncology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas 75390, USA.

PMID: 12718890
DOI: 10.1016/s1097-2765(03)00101-1

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Arginine / genetics
Arginine / metabolism
Chromosomal Proteins, Non-Histone*
Cytokines / genetics
Cytokines / metabolism
Cytokines / pharmacology
Eukaryotic Cells / enzymology*
Gene Expression Regulation, Viral / genetics
HIV-1 / genetics
HIV-1 / metabolism
HeLa Cells
Humans
Methylation
Mutation / genetics
Promoter Regions, Genetic / genetics
Protein Methyltransferases / genetics
Protein Methyltransferases / metabolism
Protein Processing, Post-Translational / genetics*
Protein-Arginine N-Methyltransferases / genetics
Protein-Arginine N-Methyltransferases / metabolism
RNA Polymerase II / genetics
RNA Polymerase II / metabolism*
Transcription, Genetic / genetics*
Transcriptional Elongation Factors / genetics
Transcriptional Elongation Factors / metabolism*

Substances

Chromosomal Proteins, Non-Histone
Cytokines
Transcriptional Elongation Factors
SPT5 transcriptional elongation factor
Arginine
Protein Methyltransferases
PRMT5 protein, human
Protein-Arginine N-Methyltransferases
RNA Polymerase II