Mediator complex regulates alternative mRNA processing via the MED23 subunit.

Mediator complex regulates alternative mRNA processing via the MED23 subunit.
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介体复合物通过MED23亚基调节替代mRNA加工。

DOI:
10.1016/j.molcel.2011.12.022
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发表时间:
2012-02-24
期刊:
影响因子:
16
通讯作者:
Wang, Gang
Wang, Gang
中科院分区:
生物学1区
文献类型:
--
作者:
Huang, Yan;Li, Wencheng;Yao, Xiao;Lin, Qi-jiang;Yin, Jing-wen;Liang, Yan;Heiner, Monika;Tian, Bin;Hui, Jingyi;Wang, Gang

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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 co-regulated genes. Taken together, these results demonstrate a crosstalk between Mediator and the splicing machinery, providing a molecular basis for coupling mRNA processing to transcription.
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