Mediator Complex Regulates Alternative mRNA Processing via the MED23 Subunit

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 recomb...

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Published inMolecular cell Vol. 45; no. 4; pp. 459 - 469
Main Authors Huang, Yan, Li, Wencheng, Yao, Xiao, Lin, Qi-jiang, Yin, Jing-wen, Liang, Yan, Heiner, Monika, Tian, Bin, Hui, Jingyi, Wang, Gang
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 24.02.2012
Subjects
Alternative Splicing
Animals
Cells, Cultured
exons
genes
Heterogeneous-Nuclear Ribonucleoprotein L - metabolism
Heterogeneous-Nuclear Ribonucleoprotein L - physiology
mass spectrometry
Mediator Complex - physiology
messenger RNA
Mice
Models, Genetic
Polyadenylation
RNA, Messenger - metabolism
transcription (genetics)
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Summary: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. ► Mediator MED23 specifically binds to a number of mRNA processing factors ► MED23 specifically interacts with hnRNP L in vitro and in vivo ► MED23 controls a subset of hnRNP L-targeted alternative mRNA processing events ► MED23 regulates hnRNP L occupancy at their coregulated genes
Bibliography:http://dx.doi.org/10.1016/j.molcel.2011.12.022
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ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2011.12.022