Transcriptional regulation of NAD metabolism in bacteria: NrtR family of Nudix-related regulators

Dmitry A. Rodionov, Jessica De Ingeniis, Chiara Mancini, Flavio Cimadamore, Hong Zhang, Andrei L. Osterman, Nadia Raffaelli

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

A novel family of transcription factors responsible for regulation of various aspects of NAD synthesis in a broad range of bacteria was identified by comparative genomics approach. Regulators of this family (here termed NrtR for Nudix-related transcriptional regulators), currently annotated as ADP-ribose pyrophosphatases from the Nudix family, are composed of an N-terminal Nudix-like effector domain and a C-terminal DNA-binding HTH-like domain. NrtR regulons were reconstructed in diverse bacterial genomes by identification and comparative analysis of NrtR-binding sites upstream of genes involved in NAD biosynthetic pathways. The candidate NrtR-binding DNA motifs showed significant variability between microbial lineages, although the common consensus sequence could be traced for most of them. Bioinformatics predictions were experimentally validated by gel mobility shift assays for two NrtR family representatives. ADP-ribose, the product of glycohydrolytic cleavage of NAD, was found to suppress the in vitro binding of NrtR proteins to their DNA target sites. In addition to a major role in the direct regulation of NAD homeostasis, some members of NrtR family appear to have been recruited for the regulation of other metabolic pathways, including sugar pentoses utilization and biogenesis of phosphoribosyl pyrophosphate. This work and the accompanying study of NiaR regulon demonstrate significant variability of regulatory strategies for control of NAD metabolic pathway in bacteria.

Original languageEnglish (US)
Pages (from-to)2047-2059
Number of pages13
JournalNucleic Acids Research
Volume36
Issue number6
DOIs
StatePublished - Apr 2008

Fingerprint

NAD
Bacteria
Adenosine Diphosphate Ribose
Regulon
Metabolic Networks and Pathways
Phosphoribosyl Pyrophosphate
Pyrophosphatases
Bacterial Genomes
Pentoses
Nucleotide Motifs
DNA
Biosynthetic Pathways
Consensus Sequence
Electrophoretic Mobility Shift Assay
Genomics
Computational Biology
Carrier Proteins
Homeostasis
Transcription Factors
Gels

ASJC Scopus subject areas

  • Genetics

Cite this

Rodionov, D. A., De Ingeniis, J., Mancini, C., Cimadamore, F., Zhang, H., Osterman, A. L., & Raffaelli, N. (2008). Transcriptional regulation of NAD metabolism in bacteria: NrtR family of Nudix-related regulators. Nucleic Acids Research, 36(6), 2047-2059. https://doi.org/10.1093/nar/gkn047

Transcriptional regulation of NAD metabolism in bacteria : NrtR family of Nudix-related regulators. / Rodionov, Dmitry A.; De Ingeniis, Jessica; Mancini, Chiara; Cimadamore, Flavio; Zhang, Hong; Osterman, Andrei L.; Raffaelli, Nadia.

In: Nucleic Acids Research, Vol. 36, No. 6, 04.2008, p. 2047-2059.

Research output: Contribution to journalArticle

Rodionov, DA, De Ingeniis, J, Mancini, C, Cimadamore, F, Zhang, H, Osterman, AL & Raffaelli, N 2008, 'Transcriptional regulation of NAD metabolism in bacteria: NrtR family of Nudix-related regulators', Nucleic Acids Research, vol. 36, no. 6, pp. 2047-2059. https://doi.org/10.1093/nar/gkn047
Rodionov DA, De Ingeniis J, Mancini C, Cimadamore F, Zhang H, Osterman AL et al. Transcriptional regulation of NAD metabolism in bacteria: NrtR family of Nudix-related regulators. Nucleic Acids Research. 2008 Apr;36(6):2047-2059. https://doi.org/10.1093/nar/gkn047
Rodionov, Dmitry A. ; De Ingeniis, Jessica ; Mancini, Chiara ; Cimadamore, Flavio ; Zhang, Hong ; Osterman, Andrei L. ; Raffaelli, Nadia. / Transcriptional regulation of NAD metabolism in bacteria : NrtR family of Nudix-related regulators. In: Nucleic Acids Research. 2008 ; Vol. 36, No. 6. pp. 2047-2059.
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