Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, Fukuura 3-9, Kanazawa-ku, Yokohama, Kanagawa, 216-0004, Japan.
Stowers Institute for Medical Research, 1000E 50th Street, Kansas City, MO, 64110, USA.
Nat Commun. 2020 Feb 26;11(1):1063. doi: 10.1038/s41467-020-14849-1.
Mediator is a coregulatory complex that regulates transcription of Pol II-dependent genes. Previously, we showed that human Mediator subunit MED26 plays a role in the recruitment of Super Elongation Complex (SEC) or Little Elongation Complex (LEC) to regulate the expression of certain genes. MED26 plays a role in recruiting SEC to protein-coding genes including c-myc and LEC to small nuclear RNA (snRNA) genes. However, how MED26 engages SEC or LEC to regulate distinct genes is unclear. Here, we provide evidence that MED26 recruits LEC to modulate transcription termination of non-polyadenylated transcripts including snRNAs and mRNAs encoding replication-dependent histone (RDH) at Cajal bodies. Our findings indicate that LEC recruited by MED26 promotes efficient transcription termination by Pol II through interaction with CBC-ARS2 and NELF/DSIF, and promotes 3' end processing by enhancing recruitment of Integrator or Heat Labile Factor to snRNA or RDH genes, respectively.
中介体是一个调控 Pol II 依赖基因转录的核心调控复合物。此前，我们发现人类中介体亚基 MED26 在募集超延伸复合物（SEC）或小延伸复合物（LEC）以调节某些基因的表达中发挥作用。MED26 发挥作用的方式是将 SEC 募集到包括 c-myc 和 LEC 到小核 RNA（snRNA）基因的蛋白编码基因。然而，MED26 如何募集 SEC 或 LEC 来调节不同的基因尚不清楚。在这里，我们提供的证据表明，MED26 募集 LEC 来调节 Cajal 体中非多聚腺苷酸化转录物（包括 snRNA 和编码复制依赖性组蛋白（RDH）的 mRNA）的转录终止。我们的发现表明，由 MED26 募集的 LEC 通过与 CBC-ARS2 和 NELF/DSIF 的相互作用，促进 Pol II 进行有效的转录终止，并分别通过增强整合酶或热不稳定因子对 snRNA 或 RDH 基因的募集，促进 3'末端加工。
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