NrdR controls differential expression of the Escherichia coli ribonucleotide reductase genes

Department of Molecular Biology & Functional Genomics, Stockholm University, SE-10691 Stockholm, Sweden; Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel

^* To whom correspondence should be addressed. Email: britt-marie.sjoberg{at}molbio.su.se. coheng{at}post.tau.ac.il.

	Abstract

E. coli possesses class Ia, class Ib and class III ribonucleotide reductases (RNR). Under standard laboratory conditions the aerobic class Ia nrdAB RNR genes are well expressed whereas the aerobic class Ib nrdEF RNR genes are poorly expressed. The class III RNR is normally expressed in microaerophilic and anerobic conditions. In this paper we show that the E. coli YbaD protein differentially regulates expression of the three sets of genes. YbaD is a homolog of the Streptomyces NrdR protein. It is not essential for growth and has been renamed NrdR. Previously the Streptomyces NrdR was shown to transcriptionally regulate RNR genes by binding to specific 16 bp sequence motifs, NrdR-boxes, located in the regulatory region of its RNR operons. All three E. coli RNR operons contain two such NrdR box motifs positioned in their regulatory regions. The NrdR boxes are located near to or overlap with the promoter elements. DNA binding experiments showed that NrdR binds to each of the upstream regulatory regions. We constructed deletions in nrdR (ybaD) and showed that they caused high level induction of transcription of the class Ib RNR genes but had a much smaller effect on induction of transcription of the class Ia and class III RNR genes. We propose a model for differential regulation of the RNR genes based on binding of NrdR to the regulatory regions. The model assumes that differences in the position of the NrdR binding sites, and in the sequences of the motifs themselves, determines the extent to which NrdR represses transcription of each RNR operon.