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Published on: September 7, 2017
Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties
Youn Tae Kwak1, Jun Guo, Shashi Prajapati
1Division of Hematology-Oncology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas 75390, USA.
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.
Insights
SPT5 methylation by PRMT1 and PRMT5 regulates its interaction with RNA polymerase II, impacting transcriptional elongation. This posttranslational modification is crucial for controlling gene expression in response to cellular and viral signals.
Area of Science:
- Molecular Biology
- Gene Regulation
- Biochemistry
Background:
- SPT5 and SPT4 are key regulators of transcriptional elongation.
- Posttranslational modifications, like phosphorylation by CDK9/cyclin T1, influence SPT5 and RNA polymerase II activity.
- Understanding SPT5 regulation is crucial for comprehending gene expression control.
Purpose of the Study:
- To investigate the role of SPT5 methylation in regulating transcriptional elongation.
- To identify the specific protein arginine methyltransferases (PRMTs) that interact with SPT5.
- To determine how SPT5 methylation affects its association with RNA polymerase II and promoter binding.
Main Methods:
- Biochemical assays were used to demonstrate the association between SPT5 and PRMT1/PRMT5.
- Methylation sites on SPT5 were identified and characterized.
- The impact of SPT5 methylation on RNA polymerase II interaction and promoter association was assessed.
Main Results:
- SPT5 was found to specifically associate with PRMT1 and PRMT5.
- Methylation of specific arginine residues in SPT5 by PRMT1/PRMT5 was demonstrated.
- SPT5 methylation was shown to regulate its interaction with RNA polymerase II and influence promoter association.
- These modifications were linked to the regulation of transcriptional elongation.
Conclusions:
- SPT5 methylation is a significant posttranslational modification controlling its transcriptional elongation function.
- This methylation process impacts SPT5's interaction with RNA polymerase II and its promoter binding.
- SPT5 methylation plays a role in regulating gene expression in response to various cellular and viral factors.
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