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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.

SUBMITTER: Huang Y 

PROVIDER: S-EPMC3288850 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Mediator complex regulates alternative mRNA processing via the MED23 subunit.

Huang Yan Y   Li Wencheng W   Yao Xiao X   Lin Qi-Jiang QJ   Yin Jing-Wen JW   Liang Yan Y   Heiner Monika M   Tian Bin B   Hui Jingyi J   Wang Gang G  

Molecular cell 20120119 4


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 col  ...[more]

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