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

Mikalai Malinouski, Nesrin M. Hasan, Yan Zhang, Javier Seravalli, Jie Lin, Andrei Avanesov, Svetlana Lutsenko and Vadim N. Gladyshev ()
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Mikalai Malinouski: Brigham and Women’s Hospital and Harvard Medical School
Nesrin M. Hasan: Johns Hopkins University
Yan Zhang: Brigham and Women’s Hospital and Harvard Medical School
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
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

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms4301

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