title: Novel mechanism of gene regulation: the protein Rv1222 of Mycobacterium tuberculosis inhibits transcription by anchoring the RNA polymerase onto DNA.
abstract: 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 either by 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. We demonstrate that the positively charged C-terminus tail of Rv1222 is responsible for anchoring RNAP on DNA, hence the protein slows down the movement of RNAP along the DNA during transcription elongation. The interaction between Rv1222 and DNA is electrostatic, thus the protein could inhibit transcription from any gene. As Rv1222 slows down the RNA synthesis, upon expression of the protein in Mycobacterium smegmatis or Escherichia coli, the growth rate of the bacteria is severely impaired. The protein does not possess any significant affinity for DNA polymerase, thus, is unable to inhibit DNA synthesis. The proposed mechanism by which Rv1222 inhibits transcription reveals a new repertoire of prokaryotic gene regulation.
authors.affiliation: Department of Chemistry, Bose Institute, 93/1 APC Road, Kolkata-700009, India.
authors.forename: Paulami
authors.initials: P
authors.lastname: Rudra
authors.affiliation: Department of Chemistry, Bose Institute, 93/1 APC Road, Kolkata-700009, India.
authors.forename: Ranjit Kumar
authors.initials: RK
authors.lastname: Prajapati
authors.affiliation: Department of Chemistry, Bose Institute, 93/1 APC Road, Kolkata-700009, India.
authors.forename: Rajdeep
authors.initials: R
authors.lastname: Banerjee
authors.affiliation: Department of Chemistry, Bose Institute, 93/1 APC Road, Kolkata-700009, India.
authors.forename: Shreya
authors.initials: S
authors.lastname: Sengupta
authors.affiliation: Department of Chemistry, Bose Institute, 93/1 APC Road, Kolkata-700009, India jayanta@jcbose.ac.in.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Mukhopadhyay
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D004269:DNA, Bacterial / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D012313:RNA / Q000096:biosynthesis; D012808:Sigma Factor / Q000037:antagonists & inhibitors; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D012808:Sigma Factor; D014157:Transcription Factors; C063202:sporulation-specific sigma factors; D012313:RNA; D012321:DNA-Directed RNA Polymerases; D004259:DNA-Directed DNA Polymerase