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Homeostatic response to hypoxia is regulated by the N-end rule pathway in plants

Nature volume 479, pages 415–418 (2011)Cite this article

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Abstract

Plants and animals are obligate aerobes, requiring oxygen for mitochondrial respiration and energy production. In plants, an unanticipated decline in oxygen availability (hypoxia), as caused by roots becoming waterlogged or foliage submergence, triggers changes in gene transcription and messenger RNA translation that promote anaerobic metabolism and thus sustain substrate-level ATP production1. In contrast to animals2, oxygen sensing has not been ascribed to a mechanism of gene regulation in response to oxygen deprivation in plants. Here we show that the N-end rule pathway of targeted proteolysis acts as a homeostatic sensor of severe low oxygen levels in Arabidopsis, through its regulation of key hypoxia-response transcription factors. We found that plants lacking components of the N-end rule pathway constitutively express core hypoxia-response genes and are more tolerant of hypoxic stress. We identify the hypoxia-associated ethylene response factor group VII transcription factors of Arabidopsis as substrates of this pathway. Regulation of these proteins by the N-end rule pathway occurs through a characteristic conserved motif at the amino terminus initiating with Met-Cys. Enhanced stability of one of these proteins, HRE2, under low oxygen conditions improves hypoxia survival and reveals a molecular mechanism for oxygen sensing in plants via the evolutionarily conserved N-end rule pathway. SUB1A-1, a major determinant of submergence tolerance in rice3, was shown not to be a substrate for the N-end rule pathway despite containing the N-terminal motif, indicating that it is uncoupled from N-end rule pathway regulation, and that enhanced stability may relate to the superior tolerance of Sub1 rice varieties to multiple abiotic stresses4.

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Figure 1: N-end rule mutants ectopically accumulate anaerobic response mRNAs and are more tolerant to hypoxia.
Figure 2: Group VII ERF transcription factors are substrates for the N-end rule pathway in vitro and in vivo.
Figure 3: HRE proteins are stabilized under low oxygen levels and confer hypoxia tolerance.

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Gene Expression Omnibus

Data deposits

The microarray data reported in this paper are deposited in Gene Expression Omnibus under accession number GSE29941 and are also tabulated in Supplementary Information.

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Acknowledgements

M.J.H., D.J.G., S.G. and C.S.C. were supported by BBSRC grant BB/G010595/1; G.W.B. by a Marie Curie International Incoming Fellowship; N.M.I. by a MARA PhD fellowship from the Malaysian government; S.C.L., T.F. and J.B.-S. by grants NSF IOS-0750811 and NIFA 2008-35100-04528. We thank S. Liddell. Rothamsted Research receives grant-aided support from the BBSRC.

Author information

Author notes

  1. Daniel J. Gibbs and Seung Cho Lee: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Plant and Crop Sciences, School of Biosciences and Centre for Plant Integrative Biology, University of Nottingham, Loughborough LE12 5RD, UK

    Daniel J. Gibbs, Nurulhikma Md Isa, Silvia Gramuglia, George W. Bassel, Cristina Sousa Correia & Michael J. Holdsworth

  2. Center for Plant Cell Biology and Department of Botany and Plant Sciences, University of California, Riverside, 92521, California, USA

    Seung Cho Lee, Takeshi Fukao & Julia Bailey-Serres

  3. UPMC Univ Paris 06, UR5-EAC 7180 CNRS, Boîte courrier 156, 4 place Jussieu, F-75005 Paris, France

    Françoise Corbineau

  4. Biological Chemistry Department, Rothamsted Research, Harpenden AL5 2JQ, UK

    Frederica L. Theodoulou

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Contributions

D.J.G., M.J.H., J.B.-S., F.C. and F.L.T. conceived and designed experiments. D.J.G., S.C.L., N.M.I., S.G., C.S.C., G.W.B., T.F. and F.C. performed the experiments. D.J.G., S.C.L., N.M.I., S.G., C.S.C., G.W.B., T.F., F.C. M.J.H., J.B-S. and F.L.T. analysed the data. M.J.H., D.J.G. and J.B.-S. wrote the manuscript.

Corresponding authors

Correspondence to Julia Bailey-Serres or Michael J. Holdsworth.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Figures

The file contains Supplementary Figures 1-5 with legends. (PDF 718 kb)

Supplementary Table 1

This file contains microarray data comparing gene expression in Col-0 (WT), prt6-1 and ate1-2 ate2-1 mutants. (XLS 310 kb)

Supplementary Table 2

This file contains a list of oligonucleotide primers used in this study. (XLS 14 kb)

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Gibbs, D., Lee, S., Md Isa, N. et al. Homeostatic response to hypoxia is regulated by the N-end rule pathway in plants. Nature 479, 415–418 (2011). https://doi.org/10.1038/nature10534

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