Structural basis for the recognition of the S2, S5-phosphorylated RNA polymerase II CTD by the mRNA anti-terminator protein hSCAF4

FEBS Letters

article

Mengqi Zhou¹  Fahad Ehsan²  Linyao Gan¹  Aiping Dong²  Yanjun Li²  Ke Liu¹  Jinrong Min¹ 

[1] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University;Structural Genomics Consortium, University of Toronto;Department of Physiology, University of Toronto

关键词: CTD interaction domain;    hSCAF4;    isothermal titration calorimetry;    phosphorylated CTD;    X-ray crystallography;   

DOI  :  10.1002/1873-3468.14256

来源: John Wiley & Sons Ltd.

【 摘 要 】

The C-terminal domain (CTD) of RNA polymerase II serves as a binding platform for numerous enzymes and transcription factors involved in nascent RNA processing and the transcription cycle. The S2, S5-phosphorylated CTD is recognized by the transcription factor SCAF4, which functions as a transcription anti-terminator by preventing early mRNA transcript cleavage and polyadenylation. Here, we measured the binding affinities of differently modified CTD peptides by hSCAF4 and solved the complex structure of the hSCAF4-CTD-interaction domain (CID) bound to a S2, S5-quadra-phosphorylated CTD peptide. Our results revealed that the S2, S5-quadra-phosphorylated CTD peptide adopts a trans conformation and is located in a positively charged binding groove of hSCAF4-CID. Although hSCAF4-CID has almost the same binding pattern to the CTD as other CID-containing proteins, it preferentially binds to the S2, S5-phosphorylated CTD. Our findings provide insight into the regulatory mechanism of hSCAF4 in transcription termination.

【 授权许可】

Unknown