Mediator Complex Regulates Alternative mRNA Processing via the MED23 Subunit

被引：132

作者：

Huang, Yan ^{[1
]}

Li, Wencheng ^{[3
]}

Yao, Xiao ^{[1
]}

Lin, Qi-jiang ^{[1
]}

Yin, Jing-wen ^{[1
]}

Liang, Yan ^{[1
]}

Heiner, Monika ^{[2
]}

Tian, Bin ^{[3
]}

Hui, Jingyi ^{[2
]}

Wang, Gang ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China

[2] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China

[3] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA

来源：

MOLECULAR CELL | 2012年 / 45卷 / 04期

基金：

中国国家自然科学基金; 美国国家卫生研究院;

关键词：

HNRNP-L; GENE-EXPRESSION; YEAST MEDIATOR; IN-VIVO; TRANSCRIPTION; BINDING; LINKS; POLYADENYLATION; RECRUITMENT; ELONGATION;

D O I：

10.1016/j.molcel.2011.12.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mediator complex is an integrative hub for transcriptional regulation. Here we show that Mediator regulates alternative mRNA processing via its MED23 subunit. Combining tandem affinity purification and mass spectrometry, we identified a number of mRNA processing factors that bind to a soluble recombinant Mediator subunit, MED23, but not to several other Mediator components. One of these factors, hnRNP L, specifically interacts with MED23 in vitro and in vivo. Consistently, Mediator partially colocalizes with hnRNP L and the splicing machinery in the cell. Functionally, MED23 regulates a subset of hnRNP L-targeted alternative splicing (AS) and alternative cleavage and polyadenylation (APA) events, as shown by minigene reporters and exon array analysis. ChIP-seq analysis revealed that MED23 can regulate hnRNP L occupancy at their coregulated genes. Taken together, these results demonstrate a crosstalk between Mediator and the splicing machinery, providing a molecular basis for coupling mRNA processing to transcription.

引用

页码：459 / 469

页数：11

共 42 条

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