Jayanta Mukhopadhyay

Jayanta Mukhopadhyay
Professor

Download CV

Previous appointments:

Howard Hughes Medical Institute/ Waksman Institute Rutgers University

Research interests:

Transcription is the first step in gene expression where most regulation occurs. RNAP core enzyme together with sigma factor(s) and/or numerous regulator(s) orchestrates the gene expression in bacteria. Our lab seeks to characterize the interactions among RNAP, sigma factors, and regulators required for various gene expressions in prokaryote, e.g. Escherichia coli, Bacillus subtilis and Mycobacterium tuberculosis. The proposed work will use integrated biophysical, biochemical and genetic approaches, along with a recombinant in vitro transcription system to address the following specific aims:

 

1. Mechanism of gene regulation by various transcriptional factors and sigma factors in prokaryote.

2. Study ‘sigma cycle’ paradigm in prokaryote

3. Identify and characterize inhibitors of M. tuberculosis gene expression. 

Contact:

Address: Chemical Sciences
Unified Academic Campus
Bose Institute
EN-80, Sector V
Bidhan Nagar
Kolkata - 700 091, India
E-Mail: jayanta[at]jcbose.ac.in
Phone: +91-33-25693295

Research:

Novel mechanism of gene regulation: the protein Rv1222 of Mycobacterium tuberculosis inhibits transcription by anchoring the RNA polymerase onto DNA.

We propose a novel mechanism of gene regulation in Mycobacterium tuberculosis where the protein Rv1222 inhibits transcription by anchoring RNA polymerase (RNAP) onto DNA. In contrast to our existing knowledge that transcriptional repressors function by either binding to DNA at specific sequences or by binding to RNAP, we show that Rv1222 mediated transcription inhibition requires simultaneous binding of the protein to both RNAP and DNA.  The proposed mechanism by which Rv1222 inhibits transcription reveals a new repertoire of prokaryotic gene regulation.

Promoter escape with bacterial two-component sigma factor suggests retention of sigma region two in the elongation complex.

The transition from the formation of RNAP-promoter open complex step to productive elongation complex step involves ‘promoter escape’ of RNAP. From the structure of RNAP, a ‘promoter escape’ model has been proposed which suggests that the interactions between sR4 and RNAP and sR4 and DNA are destabilized upon transition to elongation. This accounts for reduced affinity of s to RNAP and stochastic release of s. Using a two- component s factor YvrI and YvrHa from Bacillus subtilis that independently contribute to the functions of sR4 and sR2 in a RNAP-promoter complex, we show that YvrI, that mimics sR4, is released gradually as transcription elongation proceeds whereas YvrHa that mimics sR2 is retained throughout the elongation complexes. Thus our result validates the proposed model for promoter escape and also suggests that promoter escape involves little or no change in the interaction of sR2 with RNAP.

Bacillus subtilis d factor functions as a transcriptional regulator 

Most bacterial RNAP contain five conserved subunits viz. 2a, b, b’ and w. However, in many gram positive bacteria, especially in fermicutes, RNAP is associated with an additional factor, called d.  Over three decades since its identification, it had been thought that d functioned as a subunit of RNAP to enhance the level of transcripts by recycling RNAP.  Performing biochemical and mutational analysis we show that Bacillus subtilis d is not a subunit of RNAP, but function as a transcriptional regulator.

Mechanism of d mediated transcription activation in Bacillus subtilis:

We propose a novel mechanism of gene regulation in Bacillus subtilis where the interaction of aCTD (C-terminal domain of a subunit) of RNA polymerase (RNAP) with d, stabilizes it at the DNA binding site and d, in turn, facilitates the open complex formation. 

Recombinant reporter assay: Using three-plasmid expression system in E. coli, We develop a recombinant reporter assay would render a new and efficient avenue to monitor the interactions among M. tuberculosis RNAP, s factors, transcription factors and their cognate promoters in vivo without the hazard of handling the  pathogenic, slow growing bacteria.



Publications:

1.      Hazra N and Mukhopadhyay J, Recent Advances in Mycobacterial Transcription: Insights Beyond the General Pathway. Journal of Bacteriology (2025) In press

2.      Butler RE, Schuller M, Jaiswal R, Mukhopadhyay J, Barber J, Hingley-Wilson S, Wasson E, Alves AC, Ahel I, and Stewart GR. Control of replication and gene expression by ADP-ribosylation of DNA in Mycobacterium tuberculosis. EMBO J (2025) doi.org/10.1038/s44318-025-00451-y

3.      Tewary A, Prajapati RK, and Mukhopadhyay J. Mechanism of δ Mediated Transcription Activation in Bacillus subtilis: Interaction with a CTD of RNA Polymerase Stabilizes d and Successively Facilitates the Open Complex Formation, Journal of Molecular Biology 435 (2023) 168366

4.      Chakraborty AK, Saha S, Kousik K, Samanta T, Gautam S, Mukhopadhyay J. A saponin-polybromophenol antibiotic (CU1) from Cassia fistula Bark Against Multi-Drug Resistant Bacteria Targeting RNA polymerase. Current Research in Pharmacology and Drug Discovery (2022) 3: 100090.

5.      Sharma S, Kumar R, Jain A, Kumar M, Gauttam R, Banerjee R, Mukhopadhyay J, Tyagi JS. Functional insights into Mycobacterium tuberculosis DevR-dependent transcriptional machinery utilizing Escherichia coli. Biochem J. (2021) 478 (16):3079-3098.

6.      Mallik R, Prasad P, Kundu A, Sachdev S, Biswas R, Dutta A, Roy A, Mukhopadhyay J, Bag SK, Chaudhuri S. Identification of genome-wide targets and DNA recognition sequence of the Arabidopsis HMG-box protein AtHMGB15 during cold stress response. Biochim Biophys Acta Gene Regul Mech. (2020) 1863(12):194644.

7.      Dutta A, Rudra P, Banik SK, Mukhopadhyay J. Evidence of robustness in a two-component system using a synthetic circuit. (2020) J Bacteriol. 202 (4) e00672-19.

8.      Bhawsinghka N, Dutta A, Mukhopadhyay J, Das Gupta SK. A transcriptomic analysis of the mycobacteriophage D29 genome reveals the presence of novel stoperator-associated promoters in its right arm, (2018) Microbiology Sep;164(9):1168-1179.

9.      Mallick Gupta A, Mukherjee S, Dutta A, Mukhopadhyay J, Bhattacharyya D, Mandal S. Identification of a suitable promoter for the sigma factor of Mycobacterium tuberculosis. (2017) Mol Biosyst 13:2370-2378

10.   Prajapati RK, Sur R, Mukhopadhyay J.  A Novel function of δ factor from Bacillus subtilis as a transcriptional repressor (2016) J Biol Chem. 291(46): 24029-24035.

11.   Datta A, Yadav V, Ghosh A, Choi J, Bhattacharyya D,. Kar R K, Ilyas H, Dutta A, An E, Mukhopadhyay J, Lee D, Sanyal K, Ramamoorthy A, and Bhunia A. Mode of Action of a Designed Antimicrobial Peptide:High Potency Against Cryptococcus neoformans. (2016) Biophysical Journal 111: 1724–1737

12.   Roy A, Dutta A, Roy D, Ganguly P, Ghosh R, Kar RK, Bhunia A, Mukhopadhyay J, and Chaudhuri S. Deciphering the role of the AT-rich interaction domain and the HMG-box domain of ARID-HMG proteins of Arabidopsis thaliana. (2106) Plant Molecular Biology 92(3):389-390.

13.   Prajapati RK, Sengupta S, Rudra P, Mukhopadhyay J. Bacillus subtilis δ Factor Functions as a Transcriptional Regulator by Facilitating the Open Complex Formation. (2016) J Biol Chem. 291(3):1064-75.

14.   Promoter escape with bacterial two-component sigma factor suggests retention of sigma region two in the elongation complex. Sengupta S, Prajapati RK, and Mukhopadhyay J. (2015) J Biol Chem. 290(47):28575-83.

15.   Rudra P, Prajapati RK, Banerjee R, Sengupta S, and Mukhopadhyay J*. Novel mechanism of gene regulation: the protein Rv1222 of Mycobacterium tuberculosis inhibits transcription by anchoring the RNA polymerase onto DNA. (2015)  Nucleic Acid Research, 43: 5855-67.

16.   Saha A, Mukhopadhyay J, Datta AB, Parrack P. Revisiting the mechanism of activation of cyclic AMP receptor protein (CRP) by cAMP in Escherichia coli: Lessons from a subunit-crosslinked form of CRP. (2015)  FEBS Letters 589: 358–363.

17.   Sharma AK, Chatterjee A, Gupta S, Banerjee R, Mandal S, Mukhopadhyay J, Basu J, Kundu M. MtrA, an essential response regulator of the MtrAB two component system regulates the  transcription of resuscitation promoting factor B (RpfB) of Mycobacterium tuberculosis. (2015) Microbiology 161(6):1271-81.

18.   Banerjee R, Rudra ., Saha A, and Mukhopadhyay J. Recombinant Reporter Assay Using Transcriptional Machinery of Mycobacterium tuberculosis. (2015) Journal of Bacteriology 197, 646-653.

19.     Banerjee R, Rudra P, Prajapati, RK, Sengupta S., and Mukhopadhyay J. Optimization of recombinant Mycobacterium tuberculosis RNA polymerase expression and purification. (2014) Tuberculosis (Edinb) 94:397-404.

20.   Polyphosphate kinase 1, a central node in the stress response network of Mycobacterium tuberculosis, connects the two-component systems MprAB, SenX3-Reg X3 and the extra-cytoplasmic function sigma factor, Sigma E. Sanyal S, Banerjee, S K Banerjee, R, Mukhopadhyay J,  Kundu, M. (2013) Microbiology 159: 2074-86. 

View More

Recognition:

    Teaching:

    Courses offered for MSc  (Life Sciences)

    Thermodynamic concept of protein-ligand interactions 


    Students:

    Image Name Designation Department Campus Contact number Email
    profile image Maitrayee Mandal Junior Research Fellow Chemical Sciences Unified info.maitrayee@gmail.com
    profile image Nilanjana Hazra Junior Research Fellow Chemistry Main nilanjana.hazra@jcbose.ac.in
    profile image Soumyadeep Mukherjee Junior Research Fellow Chemical Sciences Unified soumya.mcb1997@gmail.com
    profile image Suravi Nandi Junior Research Fellow Chemistry Unified snb9496@gmail.com

    Former:

    Current members:

    1. Ritu Jaiswal, CSIR-SRF,

    2.Madhurima Chatterjee, DST Inspire Fellow,

    3. Nilanjana Hazra, Institute Fellow, SRF

    4. Suravi Nandi, UGC-SRF

    5. Maitreyee Mondal, UGC-JRF

    6.  Aniruddha Tewary, RA

    Past members:

    1.   Rajdeep Banerjee (2009-2014); Ph. D awarded 2014, current position: Post-doctoral fellow at Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health

    2.   Paulami Rudra (2009-2015); Ph.D awarded 2016, current position: Post-doctoral fellow at  NYSDOH Wadsworth Center , U of Albany School of Pub Health , Albany.

    3.   Ranjit  Kumar Prajapati (2009-2015) Ph.D awarded 2016, current position: Post-doctoral fellow at Department of Biochemistry and Food Chemistry, University of Turku, Finland

    4.   Shreya Sengupta (2009-2015) Ph.D awarded 2016, current position: Application Specialist at MNC

    6. Arkajyoti Dutta (2014-2020) Ph. D awarded 2021. current postion: Assistant Professor, VIT, Vellore, India

    7. Aniruddha Tewary  (2017-2024) Ph. D awarded 2025. current postion:Research Associate, Bose Institute

    8. Sourajit Saha (2017-2024) Thesis Submitted 2024. current postion: Field Application Specialist Proteogen Biosciences (India) Private Limited

    Group News: