Structural Basis of Three Different Transcription Activation Strategies Adopted by a Single Regulator SoxS

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2022 Oct 16

PMID 36243985

Authors

Jing Shi

Lu Wang

Aijia Wen

Fulin Wang

Yuqiong Zhang

Libing Yu

Fangfang Li

Yuanling Jin

Zhenzhen Feng

Jiacong Li

Yujiao Yang

Fei Gao

Yu Zhang

Yu Feng

Shuang Wang

Wei Zhao

Wei Lin

Affiliations

Soon will be listed here.

Abstract

Transcription activation is established through extensive protein-protein and protein-DNA interactions that allow an activator to engage and remodel RNA polymerase. SoxS, a global transcription activator, diversely regulates subsets of stress response genes with different promoters, but the detailed SoxS-dependent transcription initiation mechanisms remain obscure. Here, we report cryo-EM structures of three SoxS-dependent transcription activation complexes (SoxS-TACI, SoxS-TACII and SoxS-TACIII) comprising of Escherichia coli RNA polymerase (RNAP), SoxS protein and three representative classes of SoxS-regulated promoters. The structures reveal that SoxS monomer orchestrates transcription initiation through specific interactions with the promoter DNA and different conserved domains of RNAP. In particular, SoxS is positioned in the opposite orientation in SoxS-TACIII to that in SoxS-TACI and SoxS-TACII, unveiling a novel mode of transcription activation. Strikingly, two universally conserved C-terminal domains of alpha subunit (αCTD) of RNAP associate with each other, bridging SoxS and region 4 of σ70. We show that SoxS interacts with RNAP directly and independently from DNA, remodeling the enzyme to activate transcription from cognate SoxS promoters while repressing transcription from UP-element containing promoters. Our data provide a comprehensive summary of SoxS-dependent promoter architectures and offer new insights into the αCTD contribution to transcription control in bacteria.

Citing Articles

Structural insights into transcription regulation of the global OmpR/PhoB family regulator PhoP from Mycobacterium tuberculosis.

Shi J, Feng Z, Song Q, Wen A, Liu T, Xu L Nat Commun. 2025; 16(1):1573.

PMID: 39948061 PMC: 11825685. DOI: 10.1038/s41467-025-56697-x.

A systematic survey of TF function in E. coli suggests RNAP stabilization is a prevalent strategy for both repressors and activators.

Guharajan S, Parisutham V, Brewster R Nucleic Acids Res. 2025; 53(4).

PMID: 39921566 PMC: 11806353. DOI: 10.1093/nar/gkaf058.

The expression of different gene constructs in Escherichia coli SM lux biosensor after exposure to drugs.

Laska G, Matejczyk M, Dauksza U Sci Rep. 2024; 14(1):31899.

PMID: 39738597 PMC: 11685396. DOI: 10.1038/s41598-024-83190-0.

Repurposing endogenous type I-E CRISPR-Cas systems for natural product discovery in Streptomyces.

Zhou Q, Zhao Y, Ke C, Wang H, Gao S, Li H Nat Commun. 2024; 15(1):9833.

PMID: 39537651 PMC: 11560957. DOI: 10.1038/s41467-024-54196-z.

Structural insights into transcription activation of the antibiotic regulatory protein, AfsR.

Shi J, Ye Z, Feng Z, Wen A, Wang L, Zhang Z iScience. 2024; 27(8):110421.

PMID: 39108719 PMC: 11301090. DOI: 10.1016/j.isci.2024.110421.

References

Hook-Barnard I, Hinton D . The promoter spacer influences transcription initiation via sigma70 region 1.1 of Escherichia coli RNA polymerase. Proc Natl Acad Sci U S A. 2009; 106(3):737-42. PMC: 2630097. DOI: 10.1073/pnas.0808133106. View

Liochev S, Hausladen A, Beyer Jr W, Fridovich I . NADPH: ferredoxin oxidoreductase acts as a paraquat diaphorase and is a member of the soxRS regulon. Proc Natl Acad Sci U S A. 1994; 91(4):1328-31. PMC: 43151. DOI: 10.1073/pnas.91.4.1328. View

Kassavetis G, Elliott T, Rabussay D, Geiduschek E . Initiation of transcription at phage T4 late promoters with purified RNA polymerase. Cell. 1983; 33(3):887-97. DOI: 10.1016/0092-8674(83)90031-4. View

Geiduschek E . Regulation of expression of the late genes of bacteriophage T4. Annu Rev Genet. 1991; 25:437-60. DOI: 10.1146/annurev.ge.25.120191.002253. View

Magnez R, Thiroux B, Taront S, Segaoula Z, Quesnel B, Thuru X . PD-1/PD-L1 binding studies using microscale thermophoresis. Sci Rep. 2017; 7(1):17623. PMC: 5732298. DOI: 10.1038/s41598-017-17963-1. View

Birch C, Davis M, Mbengi L, Zuber P . Exploring the Amino Acid Residue Requirements of the RNA Polymerase (RNAP) α Subunit C-Terminal Domain for Productive Interaction between Spx and RNAP of Bacillus subtilis. J Bacteriol. 2017; 199(14). PMC: 5494735. DOI: 10.1128/JB.00124-17. View

Chen J, Chiu C, Gopalkrishnan S, Chen A, Olinares P, Saecker R . Stepwise Promoter Melting by Bacterial RNA Polymerase. Mol Cell. 2020; 78(2):275-288.e6. PMC: 7166197. DOI: 10.1016/j.molcel.2020.02.017. View

Autour A, Jeng S, Cawte A, Abdolahzadeh A, Galli A, Panchapakesan S . Fluorogenic RNA Mango aptamers for imaging small non-coding RNAs in mammalian cells. Nat Commun. 2018; 9(1):656. PMC: 5811451. DOI: 10.1038/s41467-018-02993-8. View

Aoyama T, TAKANAMI M, Ohtsuka E, Taniyama Y, Marumoto R, Sato H . Essential structure of E. coli promoter: effect of spacer length between the two consensus sequences on promoter function. Nucleic Acids Res. 1983; 11(17):5855-64. PMC: 326322. DOI: 10.1093/nar/11.17.5855. View

10.

Saecker R, Record Jr M, deHaseth P . Mechanism of bacterial transcription initiation: RNA polymerase - promoter binding, isomerization to initiation-competent open complexes, and initiation of RNA synthesis. J Mol Biol. 2011; 412(5):754-71. PMC: 3440003. DOI: 10.1016/j.jmb.2011.01.018. View

11.

Niu W, Kim Y, Tau G, Heyduk T, Ebright R . Transcription activation at class II CAP-dependent promoters: two interactions between CAP and RNA polymerase. Cell. 1996; 87(6):1123-34. PMC: 4430116. DOI: 10.1016/s0092-8674(00)81806-1. View

12.

Lilic M, Darst S, Campbell E . Structural basis of transcriptional activation by the Mycobacterium tuberculosis intrinsic antibiotic-resistance transcription factor WhiB7. Mol Cell. 2021; 81(14):2875-2886.e5. PMC: 8311663. DOI: 10.1016/j.molcel.2021.05.017. View

13.

Busby S, Ebright R . Transcription activation by catabolite activator protein (CAP). J Mol Biol. 1999; 293(2):199-213. DOI: 10.1006/jmbi.1999.3161. View

14.

Decker K, Hinton D . Transcription regulation at the core: similarities among bacterial, archaeal, and eukaryotic RNA polymerases. Annu Rev Microbiol. 2013; 67:113-39. DOI: 10.1146/annurev-micro-092412-155756. View

15.

Blatter E, Ross W, Tang H, Gourse R, Ebright R . Domain organization of RNA polymerase alpha subunit: C-terminal 85 amino acids constitute a domain capable of dimerization and DNA binding. Cell. 1994; 78(5):889-96. DOI: 10.1016/s0092-8674(94)90682-3. View

16.

Shi J, Wen A, Zhao M, You L, Zhang Y, Feng Y . Structural basis of σ appropriation. Nucleic Acids Res. 2019; 47(17):9423-9432. PMC: 6755090. DOI: 10.1093/nar/gkz682. View

17.

Lara-Gonzalez S, Dantas Machado A, Rao S, Napoli A, Birktoft J, Di Felice R . The RNA Polymerase α Subunit Recognizes the DNA Shape of the Upstream Promoter Element. Biochemistry. 2020; 59(48):4523-4532. PMC: 8100869. DOI: 10.1021/acs.biochem.0c00571. View

18.

Pettersen E, Goddard T, Huang C, Couch G, Greenblatt D, Meng E . UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem. 2004; 25(13):1605-12. DOI: 10.1002/jcc.20084. View

19.

Duval V, Lister I . MarA, SoxS and Rob of - Global regulators of multidrug resistance, virulence and stress response. Int J Biotechnol Wellness Ind. 2014; 2(3):101-124. PMC: 4031692. DOI: 10.6000/1927-3037.2013.02.03.2. View

20.

Hao M, Ye F, Jovanovic M, Kotta-Loizou I, Xu Q, Qin X . Structures of Class I and Class II Transcription Complexes Reveal the Molecular Basis of RamA-Dependent Transcription Activation. Adv Sci (Weinh). 2021; 9(4):e2103669. PMC: 8811837. DOI: 10.1002/advs.202103669. View