Reciprocity between O-GlcNAc and O-Phosphate on the Carboxyl Terminal Domain of RNA Polymerase II
详细信息 查看全文
- 作者：Frank I. Comer and Gerald W. Hart
- 刊名：Biochemistry
- 出版年：2001
- 出版时间：July 3, 2001
- 年：2001
- 卷：40
- 期：26
- 页码：7845 - 7852
- 全文大小：106K
- 年卷期：v.40,no.26(July 3, 2001)
- ISSN：1520-4995
文摘
The carboxyl terminal domain of RNA polymerase II has multiple essential roles in transcriptioninitiation, promoter clearance, transcript elongation, and the recruitment of the RNA processing machinery.Specific phosporylation events are associated with the spatial and temporal coordination of these differentactivities. The CTD is also modified by 
-O-linked GlcNAc on a subset of RNA Pol II molecules. Usingsynthetic CTD substrates, we show here that O-GlcNAc and phosphate modification of the CTD aremutually exclusive at the level of the enzymes responsible for their addition. In addition, we show thatO-GlcNAc transferase and CTD kinase have different CTD repeat requirements for enzymatic activity.The Km values of the two enzymes for CTD substrates are in a similar range, indicating that neitherenzyme has a distinct kinetic advantage. Thus, the in vivo regulation of O-GlcNAc and phosphatemodification of the CTD may involve the differential association of these two enzymes with the CTD atspecific stages during the transcription cycle. Furthermore, direct competition between OGT and CTDkinase in vivo could generate multiple functionally distinct isoforms of RNA Pol II. Taken together,these results suggest that O-GlcNAc may give rise to additional functional states of RNA Pol II and maycoordinate with phosphorylation to regulate class II gene transcription.
-O-linked GlcNAc on a subset of RNA Pol II molecules. Usingsynthetic CTD substrates, we show here that O-GlcNAc and phosphate modification of the CTD aremutually exclusive at the level of the enzymes responsible for their addition. In addition, we show thatO-GlcNAc transferase and CTD kinase have different CTD repeat requirements for enzymatic activity.The Km values of the two enzymes for CTD substrates are in a similar range, indicating that neitherenzyme has a distinct kinetic advantage. Thus, the in vivo regulation of O-GlcNAc and phosphatemodification of the CTD may involve the differential association of these two enzymes with the CTD atspecific stages during the transcription cycle. Furthermore, direct competition between OGT and CTDkinase in vivo could generate multiple functionally distinct isoforms of RNA Pol II. Taken together,these results suggest that O-GlcNAc may give rise to additional functional states of RNA Pol II and maycoordinate with phosphorylation to regulate class II gene transcription.