title: Mediator complex regulates alternative mRNA processing via the MED23 subunit.
abstract: 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.
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Wencheng
authors.initials: W
authors.lastname: Li
authors.forename: Xiao
authors.initials: X
authors.lastname: Yao
authors.forename: Qi-Jiang
authors.initials: QJ
authors.lastname: Lin
authors.forename: Jing-Wen
authors.initials: JW
authors.lastname: Yin
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.forename: Monika
authors.initials: M
authors.lastname: Heiner
authors.forename: Bin
authors.initials: B
authors.lastname: Tian
authors.forename: Jingyi
authors.initials: J
authors.lastname: Hui
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002478:Cells, Cultured; D034664:Heterogeneous-Nuclear Ribonucleoprotein L / Q000378:metabolism / Q000502:physiology; D056892:Mediator Complex / Q000502:physiology*; D051379:Mice; D008957:Models, Genetic; D026723:Polyadenylation; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D034664:Heterogeneous-Nuclear Ribonucleoprotein L; C541034:Med23 protein, mouse; D056892:Mediator Complex; D012333:RNA, Messenger