title: Rv0494 is a starvation-inducible, auto-regulatory FadR-like regulator from Mycobacterium tuberculosis.
abstract: Fatty acid metabolism plays an important role in the survival and pathogenesis of Mycobacterium tuberculosis. Lipids are assumed to be the major source of energy during dormancy. Here, we report the characterization of a starvation-inducible, lipid-responsive transcriptional regulator, Rv0494, divergently transcribed from the Rv0493c probable operon. The striking difference in the transcriptional regulatory apparatus between mycobacteria and other well-studied organisms, such as Escherichia coli, is the organization of mycobacterial promoters. Mycobacterial promoters have diverse architectures and most of these promoters function inefficiently in E. coli. In this study, we characterized the promoter elements of Rv0494 along with the sigma factors required for transcription initiation. Rv0494 promoter activity increased under nutrient starvation conditions and was transcribed via two promoters: the promoter proximal to the translational start site was active under standard growth conditions, whilst both promoters contributed to the increased activity seen during starvation, with the major contribution from the distal promoter. Furthermore, Rv0494 translation initiated at a codon located 9 bp downstream of the annotated start codon. Rv0494 bound to its upstream sequence to auto-regulate its own expression; this binding was responsive to long-chain fatty acyl-CoA molecules. We further report Rv0494-mediated transcriptional regulation of the Rv2326c gene - a probable transmembrane ATP-binding transporter encoding gene.
authors.affiliation: Computational and Functional Genomics Group, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana 500001, India.
authors.forename: Suhail
authors.initials: S
authors.lastname: Yousuf
authors.affiliation: Computational and Functional Genomics Group, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana 500001, India.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Angara
authors.affiliation: Computational and Functional Genomics Group, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana 500001, India Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Gachibowli, Telangana 500046, India.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Vindal
authors.affiliation: Computational and Functional Genomics Group, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana 500001, India akash@cdfd.org.in.
authors.forename: Akash
authors.initials: A
authors.lastname: Ranjan
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D005227:Fatty Acids / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism*; D009876:Operon; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D005227:Fatty Acids