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Genome-wide RNAi ionomics screen reveals new genes and regulation of human trace element metabolism

Author

Listed:
  • Mikalai Malinouski

    (Brigham and Women’s Hospital and Harvard Medical School
    University of Nebraska-Lincoln)

  • Nesrin M. Hasan

    (Johns Hopkins University)

  • Yan Zhang

    (Brigham and Women’s Hospital and Harvard Medical School
    Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences)

  • Javier Seravalli

    (University of Nebraska-Lincoln)

  • Jie Lin

    (Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences
    Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences)

  • Andrei Avanesov

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Svetlana Lutsenko

    (Johns Hopkins University)

  • Vadim N. Gladyshev

    (Brigham and Women’s Hospital and Harvard Medical School)

Abstract

Trace elements are essential for human metabolism and dysregulation of their homoeostasis is associated with numerous disorders. Here we characterize mechanisms that regulate trace elements in human cells by designing and performing a genome-wide high-throughput siRNA/ionomics screen, and examining top hits in cellular and biochemical assays. The screen reveals high stability of the ionomes, especially the zinc ionome, and yields known regulators and novel candidates. We further uncover fundamental differences in the regulation of different trace elements. Specifically, selenium levels are controlled through the selenocysteine machinery and expression of abundant selenoproteins; copper balance is affected by lipid metabolism and requires machinery involved in protein trafficking and post-translational modifications; and the iron levels are influenced by iron import and expression of the iron/haeme-containing enzymes. Our approach can be applied to a variety of disease models and/or nutritional conditions, and the generated data set opens new directions for studies of human trace element metabolism.

Suggested Citation

  • Mikalai Malinouski & Nesrin M. Hasan & Yan Zhang & Javier Seravalli & Jie Lin & Andrei Avanesov & Svetlana Lutsenko & Vadim N. Gladyshev, 2014. "Genome-wide RNAi ionomics screen reveals new genes and regulation of human trace element metabolism," Nature Communications, Nature, vol. 5(1), pages 1-11, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4301
    DOI: 10.1038/ncomms4301
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    Cited by:

    1. Eva Nývltová & Jonathan V. Dietz & Javier Seravalli & Oleh Khalimonchuk & Antoni Barrientos, 2022. "Coordination of metal center biogenesis in human cytochrome c oxidase," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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