Basic mechanisms that regulate RNA polymerase II transcription
The Pre-Initiation Complex (PIC), which consists of Mediator, TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH, and RNA polymerase II (pol II), governs the expression of all protein-coding and most non-coding RNA genes in the human genome and is approximately 4.0ÌýMDa in size. ÌýMediator and TFIID, each approximately 1.4 MDa, represent major assemblies within the PIC and work to control PIC function in ways that are just beginning to be understood. ÌýThe structural features of Mediator and TFIID (conformationally dynamic, extended shape) coupled with their large size (e.g. human Mediator approximately 320 x 180 x 160 Ã…) provide an extensive surface for interaction with other proteins or nucleic acids. ÌýTFIIH is also a large (10 subunit, 0.5MDa) and structurally dynamic protein complex. ÌýLike Mediator and TFIID, TFIIH is required for pol II transcription, genome-wide. ÌýNotably, Mediator, TFIID, and TFIIH appear to function cooperatively within the PIC; however, the molecular mechanisms underlying their coordinated or synergistic function remain poorly understood. Ìý Our lab is using a variety of biochemical, cellular, and biophysical methods to better define how Mediator, TFIID, and TFIIH work together with other PIC components to regulate pol II transcription initiation, promoter-proximal pausing, and elongation.
Recent publications related to this topic:
Luyties, O; Sanford, L; Rodino, J; Nagel, M; Jones, T; Rimel, JK; Ebmeier, CC; Palacio, M; Shelby, GS; Cozzolino, K; Brennan, F; Hartzog, A; Saucedo, MB; Watts, LP; Spencer, S; Kugel, JF; Dowell, RD; Taatjes DJ. Multi-omics and biochemical reconstitution reveal CDK7-dependent mechanisms controlling RNA polymerase II function at gene 5'- and 3'-ends. Cell Rep 2025, 44: 115904.
Nagel, M; Taatjes, DJ. Regulation of RNA polymerase II transcription through re-initiation and bursting. Mol Cell 2025, 85: 1907-1919.
Jones, T; Feng, J; Luyties, O; Cozzolino, K; Sanford, L; Rimel, JK; Ebmeier, CC; Shelby, GS; Watts, LP; Rodino, J; Rajagopal, N; Hu, S; Brennan, F; Maas, ZL; Alnemy, S; Richter, WF; Koh, AF; Cronin, NB; Madduri, A; Das, J; Cooper, E; Hamman, KB; Carulli, JP; Allen, MA; Spencer, S; Kotecha, A; Marineau, J; Greber, BJ; Dowell, RD; Taatjes DJ. TFIIH kinase CDK7 drives cell proliferation through a common core transcription factor network. Sci Adv 2025, 11: eadr9660.Ìý
Richter, WF; Taatjes DJ. Changing structures, changing paradigms: NELF helps regulate paused or elongating RNA Polymerase II. Mol Cell 2024, 84: 1180 - 1182. Ìý
Nayak, S; Taatjes DJ. SnapShot: Mediator Complex Structure.ÌýCellÌý2022, 185: 3458.
Bassett, J; Rimel, JK; Basu, S; Basnet, P; Luo, J; Engel, KL; Nagel, MT; Woyciehowsky, A; Ebmeier, CC; Kaplan, CD; Taatjes, DJ; Ranish, JA. Systematic mutagenesis of TFIIH subunit p52/Tfb2 identifies residues required for XPB/Ssl2 subunit function and genetic interactions with TFB6.ÌýJ Biol ChemÌý2022, 102433.
Richter, WF; Nayak, S; Iwasa, J; Taatjes, DJ. The Mediator complex as a master regulator of transcription by RNA polymerase II.ÌýNat Rev Mol Cell BiolÌý2022, 23: 732 - 749.
Luyties, O; Taatjes, DJ.ÌýÌýThe Mediator kinase module: an interface between cell signaling and transcription.ÌýTrends Biochem SciÌý2022, 47: 314 - 327.ÌýÌý
Palacio, M; Taatjes DJ.ÌýMerging established mechanisms with new insights: Condensates, hubs, and the regulation of RNA polymerase II transcription.ÌýJ Mol BiolÌý2022, 433: 167216.ÌýÌý
Schier, A; Taatjes, DJ.ÌýEverything at once: Cryo-EM yields remarkable insights about human RNA polymerase II transcription.ÌýNat Struct Mol BiolÌý2021, 28: 540 - 543.ÌýÌý
Tomko, EJ; Luyties, O; Rimel, JK; Tsai, C; Fuss, JO; Fishburn, J; Hahn, S; Tsutakawa, SE; Taatjes, DJ; Galburt, EA.ÌýThe role of XPB/Ssl2 dsDNA translocation processivity in transcription start-site scanning.ÌýJ Mol BiolÌý2021;Ìý433: 166813.
Rimel, JK; Poss, ZC; Erickson, B; Maas, ZL; Ebmeier, CC; Johnson, JL; Decker, T-M; Yaron, TM; Bradley, MJ; Hamman, KB; Hu, S; Malojcic, G; Marineau, JJ; White, PW; Brault, M.; Tao, L.; DeRoy, P; Clavette, C; Nayak, S; Damon, LJ; Kaltheuner, IH; Bunch, H; Cantley, LC; Geyer, M; Iwasa, J; Dowell, RD; Bentley, DL; Old WM; Taatjes, DJ.ÌýÌýSelective inhibition of CDK7 reveals high-confidence targets and novel mechanisms for TFIIH function in transcription.ÌýGenes DevÌý2020; 34: 1452 –Ìý1473.
Fant, CB; Levandowski, CB; Gupta, K; Maas, ZL; Moir, JT; Rubin, JD; Sawyer, A; Esbin, M; Rimel, JK; Luyties, O; Marr, MT; Berger, I; Dowell, RD; Taatjes, DJ. TFIID enables RNA polymerase II promoter-proximal pausing.ÌýMol CellÌý2020, 78: 785 – 793.Ìý
Schier, AC; Taatjes, DJ. Structure and mechanism of the RNA polymerase II transcription machinery.ÌýGenes Dev.Ìý2020, 34: 465 – 488.Ìý
Guo, YE; Manteiga, JC; Henninger, J; Sabari, BR; Dall'Agnese, A; Hannett, NM; Spille, J-H; Afeyan, LK; Zamudio, AV;ÌýÌýShrinivas, K; Abraham, BJ; Boija, A; Decker, TM; Rimel, JK; Fant, CB; Lee, TI; Cisse, II; Sharp, PA; Taatjes, DJ; Young, RA. RNA polymerase II phosphorylation regulates a switch between transcriptional and splicing condensates.ÌýNatureÌý2019, 572: 543 – 548.
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