The role of Mediator and Little Elongation Complex in transcription termination
The role of Mediator and Little Elongation Complex in transcription termination
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介体和小延伸复合物在转录终止中的作用
DOI：
10.1038/s41467-020-14849-1
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发表时间：
2020
影响因子：
16.6
通讯作者：
Florens
中科院分区：
文献类型：
--
作者：
Takahashi H;Ranjan A;Chen S;Suzuki H;Shibata M;Hirose T;Hirose H;Sasaki K;Abe R;Chen K;He Y;Zhang Y;Takigawa I;Tsukiyama T;Watanabe M;Fujii S;Iida M;Yamamoto J;Yamaguchi Y;Suzuki Y;Matsumoto M;Nakayama KI;Washburn P;Saraf A;Florens
介体是一种共调节复合物，调节Pol II依赖基因的转录。以前，我们发现人Mediator亚基MED 26在超延伸复合物（SEC）或小延伸复合物（LEC）的募集中起作用，以调节某些基因的表达。MED 26在将SEC募集到蛋白质编码基因（包括c-myc）和将LEC募集到小核RNA（snRNA）基因中起作用。然而，MED 26如何参与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，MED 26招募LEC调节非多聚腺苷酸化的转录本，包括snRNAs和mRNA编码的复制依赖性组蛋白（RDH）在卡哈尔体的转录终止。我们的研究结果表明，被MED 26募集的LEC通过与CBC-ARS 2和NELF/DSIF的相互作用促进Pol II的有效转录终止，并通过增强整合子或热不稳定因子分别向snRNA或RDH基因的募集来促进3′端加工。
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 includingc-mycand 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.