RelE, a global inhibitor of translation, is activated during nutritional stress
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, OU, Campusvej 55, DK-5230 Odense M, Denmark
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Edited by Carol A. Gross, University of California, San Francisco, CA, and approved October 4, 2001 (received for review June 28, 2001)
Abstract
The stringent response is defined as the physiological changes elicited by amino acid starvation. Many of these changes depend on the regulatory nucleotide ppGpp (guanosine tetraphosphate) synthesized by RelA (ppGpp synthetase I), the relA-encoded protein. The second rel locus of Escherichia coli is called relBE and encodes RelE cytotoxin and RelB antitoxin. RelB counteracts the toxic effect of RelE. In addition, RelB is an autorepressor of relBE transcription. Here we reveal a ppGpp-independent mechanism that reduces the level of translation during amino acid starvation. Artificial overexpression of RelE severely inhibited translation. During amino acid starvation, the presence of relBE caused a significant reduction in the poststarvation level of translation. Concomitantly, relBE transcription was rapidly and strongly induced. Induction of transcription occurred independently of relA and spoT (encoding ppGpp synthetase II), but instead depended on Lon protease. Consistently, Lon was required for degradation of RelB. Replacement of the relBE promoter with a LacI-regulated promoter indicated that strong and ongoing transcription of relBE is required to maintain a proper RelB:RelE ratio during starvation. Thus relBE may be regarded as a previously uncharacterized type of stress-response element that reduces the global level of translation during nutritional stress.
Footnotes
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↵ * To whom reprint requests should be addressed. E-mail: kgerdes{at}bmb.sdu.dk.
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This paper was submitted directly (Track II) to the PNAS office.
- Abbreviations:
- aa,
- amino acid;
- wt,
- wild type;
- ppGpp,
- guanosine tetraphosphate;
- IPTG,
- isopropyl β-d-thiogalactoside;
- SHT,
- serine hydroxamate;
- Cml,
- chloramphenicol
- Copyright © 2001, The National Academy of Sciences
