Featured Publication
Structural basis of the human transcriptional Mediator regulated by its dissociable kinase module.
The eukaryotic transcriptional Mediator comprises a large core (cMED) and a dissociable CDK8 kinase module (CKM). cMED recruits RNA polymerase II (RNA Pol II) and promotes pre-initiation complex formation in a manner repressed by the CKM through mechanisms presently unknown. Herein, we report cryoelectron microscopy structures of the complete human Mediator and its CKM. The CKM binds to multiple regions on cMED through both MED12 and MED13, including a large intrinsically disordered region (IDR) in the latter. (Read more...)
Structural basis of a transcription pre-initiation complex on a divergent promoter
Gorbea et al. solved the cryo-EM structure of a yeast Mediator-pre- initiation complex assembled on a divergent promoter. The complex dimerizes through a homodimeric activator protein and requires late general transcription factors for core promoter commitment. These findings open new avenues to determine the mechanisms of divergent transcription widespread in eukaryotes. Read more...
Structure and non-canonical Cdk8 activation mechanism within an Argonaute-containing Mediator kinase module
A cryo–electron microscopy structure of Saccharomyces cerevisiae CKM explains the mechanism of Med12-dependent Cdk8 activation and provide a novel potential drug target for uterine leiomyoma. Read more...
All Publications
2024
1. Structural basis of the human transcriptional Mediator complex modulated by its dissociable Kinase module
BioRxiv 2024
2. Structures and Compositional Dynamics of Mediator in Transcription Regulation
Tao Li, Ti-chun Chao, Kuang-Lei Tsai.
Current Opinion in Structural Biology 2024
3. Structural basis of the human transcriptional Mediator regulated by its dissociable Kinase module
Ti-Chun Chao, Shin-Fu Chen, Hee Jong Kim, Hui-Chi Tang, Hsiang-Ching Tseng, An Xu, Leon Palao III, Subash Khadka, Tao Li,Mo-Fan Huang, Dung-Fang Lee, Kenji Murakami,* Thomas G. Boyer,* and Kuang-Lei Tsai
Molecular Cell 2024
2023
1. Unveiling the Noncanonical Activation Mechanism of CDKs: Insights from Recent Structural Studies
Tao Li, Hui-chi Tang, Kuang-Lei Tsai.
Frontiers in Molecular Biosciences-Structural Biology Volume 10 - 2023
2. Structural basis of a transcription pre-initiation complex on a divergent promoter
Molecular cell 83, 1–15, 2023
Subash Khadka, Claire Sun, Lindsey Barron, Robert Schenken, Nicholas Stansbury, Shin-Fu Chen, Kuang-Lei Tsai, Ron Firestein, Thomas Boyer
Journal of Biological Chemistry 299(3), S198-S199,2023
2022
1. The Hypoxia-Adenosine Link during Myocardial Ischemia—Reperfusion Injury.
W Ruan, X Ma, IH Bang, Y Liang, JD Muehlschlegel, KL Tsai, TW Mills, X Yuan, HK Eltzschig
Biomedicines 10(8), 1939,2022
2. Hereditary retinoblastoma iPSC model reveals aberrant spliceosome function driving bone malignancies.
J Tu, Z Huo, Y Yu, D Zhu, A Xu , MF Huang, R Hu, R Wang, JA. Gingold, YH Chen, KL Tsai, NR. Forcioli-Conti, SXL. Huang, TR, J Su, DA. Bazer, PJ Jason T. Yustein, LL Wang, MC Hung, Z Zhao, CD. Huff, J Shen, R Zhao, Dung-Fang Lee.
PNAS, 119 (16) e2117857119,2022
2021
F Xiong, R Wang, JH Lee, S Li, SF Chen, Z Liao, LA Hasani, PT Nguyen, X Zhu, J Krakowiak, DF Lee, LH, KL Tsai, Y Liu,
W Li
Cell Research volume 31, pages 861–885, 2021
2. A noncoding RNA modulator potentiates phenylalanine metabolism in mice
Y Li, Z Tan, Y Zhang, ZZ hang, Q Hu, K Liang, Y Jun, Y Ye, YC Li, C Li, L Liao, J Xu, ZX, Y Pan, SS Chatterjee, TK Nguyen, H Hsiao, SD Egranov, NP utluri, C Coarfa, DH Hawke, PH Gunaratne, KL Tsai, L Han, MC Hung, GA Calin, F Namour, JL Guéant, A Muntau, N Blau, VR Sutton, M Schiff, F Feillet, S Zhang, C Lin, L Yang
Science, 373 (6555)662-673, 2021
L Barron, S Khadka, R Schenken, L He, J Blenis, J Blagg, SF Chen, KL Tsai, TG Boyer.
F&S Science, 2(4) 383-395, 2021
4. Structure of TFIIK for phosphorylation of CTD of RNA polymerase II.
van Eeuwen T, Li T, Kim HJ, Gorbea Colón JJ, Parker MI, Dunbrack RL, Garcia BA, Tsai KL*, Murakami K*.
Science Advances, 7(15):eabd4420,2021
JH Lee, R Wang, F Xiong, J Krakowiak, Z Liao, PT Nguyen, EV Moroz-Omori, J Shao, X Zhu, MJ Bolt, H Wu, PK Singh, M Bi, CJ Shi, N Jamal, G Li, R Mistry, SY Jung, KL Tsai, JC Ferreon, F Stossi, A Caflisch, Z Liu, MA Mancini, W Li.
Mol Cell. Aug 19;81(16):3368-3385.e9, 2021
6. Comparative parallel analysis of RNA ends identifies mRNA substrates of a tRNA splicing endonuclease-initiated mRNA decay pathway.
JE Hurtig, MA Steiger, VK Nagarajan, T Li, TC Chao, KL Tsai, AV Hoof. PNAS, 118 (10) e2020429118,2021
7. Structure and non-canonical Cdk8 activation mechanism within an Argonaute-containing Mediator kinase module
YC Li; TC Chao; HJ Kim; T Cholko; SF Chen; K Nakanishi; CE Chang; K Murakami; B Garcia; T Boyer*; KL Tsai* Science Advances, Jan 15;7(3):eabd4484, 2021
1. 3.3-Å resolution cryo-EM structure of human ribonucleotide reductase with substrate and allosteric regulators bound
Brignole E*, KL Tsai*, Chittuluru J, Li H, Penczek P, Stubbe J, Drennan C, Asturias FJ. (*Authors contributed equally)
eLife, 7:e31502, 2018
2. Mediator structure and rearrangements required for holoenzyme formation
KL Tsai, X Yu, S Gopalan, TC Chao, Y Zhang, L Florens, MP Washburn, ...
Nature, 544(7649), 196-201, 2017
3. Role for the MED21-MED7 Hinge in assembly of the Mediator-RNA polymerase II holoenzyme
S Sato, C Tomomori-Sato, KL Tsai, X Yu, M Sardiu, A Saraf, ...
Journal of Biological Chemistry 291 (52), 26886-26898, 2016
4. Structure of an RNA polymerase II preinitiation complex
K Murakami*, KL Tsai*, N Kalisman, DA Bushnell, FJ Asturias, RD Kornberg
Proceedings of the National Academy of Sciences 112 (44), 13543-13548, 2015
5. Structure of a designed protein cage that self-assembles into a highly porous cube
YT Lai, E Reading, GL Hura, KL Tsai, A Laganowsky, FJ Asturias, ...
Nature chemistry 6 (12), 1065-1071, 2014
6. Reconstitution of the augmin complex provides insights into its architecture and function
KC Hsia, EM Wilson-Kubalek, A Dottore, Q Hao, KL Tsai, S Forth, ...
Nature cell biology 16 (9), 852, 2014
7. Subunit architecture and functional modular rearrangements of the transcriptional mediator complex
KL Tsai, C Tomomori-Sato, S Sato, RC Conaway, JW Conaway, ...
Cell 157 (6), 1430-1444, 2014
8. A conserved Mediator–CDK8 kinase module association regulates Mediator–RNA polymerase II interaction
KL Tsai, S Sato, C Tomomori-Sato, RC Conaway, JW Conaway, ...
Nature structural & molecular biology 20 (5), 611-619, 2013
9. Structure and flexibility of nanoscale protein cages designed by symmetric self-assembly
YT Lai, KL Tsai, MR Sawaya, FJ Asturias, TO Yeates
Journal of the American Chemical Society 135 (20), 7738-7743, 2013
10. Architecture of the Mediator head module
T Imasaki, G Calero, G Cai, KL Tsai, K Yamada, F Cardelli, ...
Nature 475 (7355), 240, 2011
11. Molecular interplay between the replicative helicase DnaC and its loader protein DnaI from Geobacillus kaustophilus
KL Tsai, YH Lo, YJ Sun, CD Hsiao
Journal of molecular biology 393 (5), 1056-1069, 2009
12. The crystal structure of a replicative hexameric helicase DnaC and its complex with single-stranded DNA
YH Lo, KL Tsai*, YJ Sun, WT Chen, CY Huang, CD Hsiao
Nucleic acids research 37 (3), 804-814, 2008
13. Crystal structure of the human FOXO3a-DBD/DNA complex suggests the effects of post-translational modification
KL Tsai, YJ Sun, CY Huang, JY Yang, MC Hung, CD Hsiao
Nucleic acids research 35 (20), 6984-6994, 2007
14. Crystal structure of the human FOXK1a-DNA complex and its implications on the diverse binding specificity of winged helix/forkhead proteins
KL Tsai, CY Huang, CH Chang, YJ Sun, WJ Chuang, CD Hsiao
Journal of Biological Chemistry 281 (25), 17400-17409