Year: 2020
Type: article
Abstract: 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.
Source: Nature Communications
Authors: Hidehisa Takahashi, Amol Ranjan, Shiyuan Chen, Hidefumi Suzuki, Mio Shibata, Tomonori Hirose, Hiroko Hirose, Kazunori Sasaki, Ryota Abe, Kai Chen, Yanfeng He, Ying Zhang, Ichigaku Takigawa, Tadasuke Tsukiyama, Masashi Watanabe, Satoshi Fujii, Midori Iida, Junichi Yamamoto, Yuki Yamaguchi, Yutaka Suzuki, Masaki Matsumoto, Keiichi I. Nakayama, Michael P. Washburn, Anita Saraf, Laurence Florens, Shigeo Sato, Chieri Tomomori-Sato, Ronald C. Conaway, Joan W. Conaway, Shigetsugu Hatakeyama
Institutions: Yokohama City University, Stowers Institute for Medical Research, Hokkaido University, Kyushu Institute of Technology, Tokyo Medical University, Tokyo Institute of Technology, The University of Tokyo, Kyushu University, Medical Institute of Bioregulation, Kyushu University, University of Kansas Medical Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,380
Funders: Naito Foundation, Uehara Memorial Foundation, Tokyo Biochemical Research Foundation, Ministry of Education, Culture, Sports, Science and Technology, Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care, Kobayashi Foundation for Cancer Research, Japan Society for the Promotion of Science
Awards: Establishment of a platform for development of tumor treatment seeds targeting a novel transcription elongation regulator Med26, Investigation for mechanisms underlying cell cycle regulation and metabolism in stem cells, Platform for Advanced Genome Science, Comprehensive identification of polyubiquitinated substrates for elucidation of the "ubiquitin code", G3924282546, Search for novel modulators of cereblon, the target of thalidomide that regulates neural stem cell proliferation and deifferentiation, Elucidation of liquid phase separation by Mediator complex and its role in transcription regulation, Elucidation of the selection mechanism of transcription termination and polyadenylation sites by using novel proteomic approach, Analysis of ubiquitin network regulation by TRIM family proteins, G6985164334, The function of RNF43 in tumorigenesis and maintaining homeostasis, Regulation of signal transduction by TRIM family proteins, Defense mechanism against lifestyle diseases by ubiquitin-like modifier UFM1, Elucidation of the relation between novel transcription regulation by Med26 and the onset of neoplastic disease, Dissecting the molecular mechanism of Wnt receptor ubiquitination by RNF43., Platform of large scale and high quality genomics and bioinformatics: Towards the advancement of genome sciences in academia, G8233826233, Analysis on the involvement of the new transcriptional elongation regulator Med26 in mixed acute leukemia, G8572344951
OpenAlex ID: W3008098792